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Zhong D, Li X, Yin Z, Chen P, Li Y, Tian J, Wang L, Liu H, Yin K, Zhu L, Kong L, Chen K, Li Y, Hong C, Wang C. Circ-ITCH promotes the ubiquitination degradation of HOXC10 to facilitate osteogenic differentiation in disuse osteoporosis through stabilizing BRCA1 mRNA via IGF2BP2-mediated m 6A modification. J Transl Med 2025; 23:376. [PMID: 40148953 PMCID: PMC11951756 DOI: 10.1186/s12967-024-06050-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/18/2024] [Accepted: 12/25/2024] [Indexed: 03/29/2025] Open
Abstract
BACKGROUND Osteogenic differentiation of bone marrow mesenchymal stem cells (BM-MSCs) facilitated by mechanical loading is a promising therapy for disuse osteoporosis (DOP), however, it is difficult to implement mechanical loading for a majority of patients. Our study aims to identify circ-ITCH-mediated novel approach to facilitate osteogenic differentiation in DOP. METHODS A rat DOP model and human BM-MSCs under microgravity condition were generated as in vivo and in vitro models of DOP, respectively. The bone mineral density (BMD) and bone parameters were examined in rats. The histological changes of bones and mineralization were monitored by H&E, Alcian blue and Alizarin red S staining. Co-IP was employed to examine the ubiquitination of HOXC10 and the interaction between HOXC10 and BRCA1. The direct associations among circ-ITCH, IGFBP2 and BRCA1 mRNA were assessed by RIP, FISH and RNA pull-down assays. RESULTS Circ-ITCH was downregulated in rat model of DOP and BM-MSCs under microgravity stimulation. Circ-ITCH overexpression promoted osteogenic differentiation in BM-MSCs under microgravity condition. The altered bone parameters, such as BMD, trabecular number (Tb.N), trabecular separation (Tb.Sp), trabecular thickness (Tb.Th), and bone microstructure in DOP rats were rescued by circ-ITCH overexpression. Mechanistically, circ-ITCH enhanced the ubiquitination degradation of HOXC10 through enhancing BRCA1 mRNA stability. Circ-ITCH directly bound to IGF2BP2 protein to stabilize BRCA1 mRNA via m6A modification, thus facilitating osteogenic differentiation in BM-MSCs under microgravity condition. CONCLUSION Circ-ITCH stabilized BRCA1 mRNA via IGF2BP2-mediated m6A modification, thereby facilitating the ubiquitination degradation of HOXC10 to promote osteogenic differentiation in DOP.
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Affiliation(s)
- Da Zhong
- Department of Orthopaedics, Xiangya Hospital of Central South University, Changsha, China
- Hunan Key Laboratory of Aging Biology, Xiangya Hospital, Central South University, Changsha, China
| | - Xi Li
- Department of Orthopaedics, Xiangya Hospital of Central South University, Changsha, China
- National Clinical Research Center of Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China
| | - Zhen Yin
- Department of Orthopaedics, Xiangya Hospital of Central South University, Changsha, China
| | - Peng Chen
- Department of Orthopaedics, Xiangya Hospital of Central South University, Changsha, China
| | - Yusheng Li
- Department of Orthopaedics, Xiangya Hospital of Central South University, Changsha, China
- National Clinical Research Center of Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China
| | - Jian Tian
- Department of Orthopaedics, Xiangya Hospital of Central South University, Changsha, China
| | - Long Wang
- Department of Orthopaedics, Xiangya Hospital of Central South University, Changsha, China
- The School of Medicine, Nankai University, Tianjin, China
| | - Hua Liu
- Department of Orthopaedics, Xiangya Hospital of Central South University, Changsha, China
| | - Ke Yin
- The First Affiliated Hospital, Department of Orthopedics, Hengyang Medical School, University of South China, Hengyang, China
| | - Lemei Zhu
- School of Public Health, Changsha Medical University, Changsha, China
| | - Lingyu Kong
- Department of Radiology, Xiangya Hospital, Central South University, Changsha, China
| | - Kunli Chen
- Department of Rehabilitation Medicine, Xiangya Hospital, Central South University, Changsha, China
| | - Yaochun Li
- Department of Rehabilitation Medicine, Xiangya Hospital, Central South University, Changsha, China
| | - Chungu Hong
- Department of Orthopedics, Movement System Injury and Repair Research Center, Xiangya Hospital, Central South University, Changsha, China
| | - Chenggong Wang
- Department of Orthopaedics, Xiangya Hospital of Central South University, Changsha, China.
- Hunan Key Laboratory of Aging Biology, Xiangya Hospital, Central South University, Changsha, China.
- National Clinical Research Center of Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China.
- Department of Orthopaedics, Xiangya Hospital of Central South University, No. 87 Xiangya Road, Changsha, Hunan Province, 410008, China.
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Limlawan P, Vacharaksa A. MicroRNA functions in osteogenic differentiation of periodontal ligament stem cells: a scoping review. FRONTIERS IN ORAL HEALTH 2025; 6:1423226. [PMID: 39959357 PMCID: PMC11825769 DOI: 10.3389/froh.2025.1423226] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/25/2024] [Accepted: 01/20/2025] [Indexed: 02/18/2025] Open
Abstract
This scoping review aimed to describe the differential microRNA (miRNA) functions in osteogenic differentiation of periodontal ligament stem cells (PDLSCs), and then analyze the potential of applying PDLSCs and miRNAs in bone regeneration. The databases of PubMed, Google Scholar and EBSCO search were performed by the 4 themes, including periodontal ligament stem cells, miRNA, osteogenic differentiation, and tissue regeneration. The original articles described miRNA functions in osteogenic differentiation of PDLSCs were identified and selected for content analyze. The articles suggested that PDLSCs have high potential in bone regeneration because of their multipotency and immunomodulation. PDLSCs are conveniently accessible and obtained from extracted teeth. However, recent evidence reported that PDLSCs of various origins demonstrate differential characteristics of osteogenic differentiation. Exosomal miRNAs of PDLSCs demonstrate a regulatory role in tissue regeneration. The properties of PDLSCs associated to miRNA functions are altered in differential microenvironmental conditions such as infection, inflammation, high-glucose environment, or mechanical force. Therefore, these factors must be considered when inflamed PDLSCs are used for tissue regeneration. The results suggested inflammation-free PDLSCs harvested from the middle third of root surface provide the best osteogenic potential. Alternatively, the addition of miRNA as a bioactive molecule also increases the success of PDLSCs therapy to enhance their osteogenic differentiation. In conclusion, Exosome-derived miRNAs play a key role in PDLSCs osteogenic differentiation during tissue regeneration. While the success of PDLSCs in tissue regeneration could be uncertain by many factors, the use of miRNAs as an adjunct is beneficial for new bone regeneration.
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Affiliation(s)
- Pirawish Limlawan
- Department of Oral Medicine, Faculty of Dentistry, Chulalongkorn University, Bangkok, Thailand
- Center of Excellence and Innovation for Oral Health and Healthy Longevity, Faculty of Dentistry, Chulalongkorn University, Bangkok, Thailand
| | - Anjalee Vacharaksa
- Research Unit on Oral Microbiology and Immunology, Faculty of Dentistry, Chulalongkorn University, Bangkok, Thailand
- Department of Microbiology, Faculty of Dentistry, Chulalongkorn University, Bangkok, Thailand
- Master of Science Program in Geriatric Dentistry and Special Patients Care, Faculty of Dentistry, Chulalongkorn University, Bangkok, Thailand
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Aranguren S, Cole H, Dargan LJ, Sarlo M, Choi S, Satapathy I, de Vasconcellos JF. Recent advances in the regulatory and non-coding RNA biology of osteogenic differentiation: biological functions and significance for bone healing. Front Cell Dev Biol 2025; 12:1483843. [PMID: 39834390 PMCID: PMC11743950 DOI: 10.3389/fcell.2024.1483843] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/20/2024] [Accepted: 12/04/2024] [Indexed: 01/22/2025] Open
Abstract
Injuries associated with contemporary life, such as automobile crashes and sports injuries, can lead to large numbers of traumatic neuromuscular injuries that are intimately associated with bone fractures. Regulatory and non-coding RNAs play essential roles in multiple cellular processes, including osteogenic differentiation and bone healing. In this review, we discuss the most recent advances in our understanding of the regulatory and non-coding RNA biology of osteogenic differentiation in stem, stromal and progenitor cells. We focused on circular RNAs, small nucleolar RNAs and PIWI-interacting RNAs and comprehensively summarized their biological functions as well as discussed their significance for bone healing and tissue regeneration.
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Guo J, Ouyang XY, Liu JR, Liu WY, Wang YB. miR-508-5p suppresses osteogenic differentiation of human periodontal ligament stem cells via targeting sex-determining region Y-related HMG-box 11. J Dent Sci 2025; 20:201-211. [PMID: 39873049 PMCID: PMC11763229 DOI: 10.1016/j.jds.2024.08.012] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/10/2024] [Revised: 08/19/2024] [Indexed: 01/30/2025] Open
Abstract
Background/Purpose The local inflammatory microenvironment created by periodontitis negatively impacts periodontal tissue regeneration, necessitating the development of methods to enhance the regenerative capacity of stem cells. This study explored the regulatory role and underlying mechanism of miR-508-5p in the osteogenic differentiation of human periodontal ligament stem cells (hPDLSCs). Materials and methods The regulatory roles of miR-508-5p in osteogenic differentiation of hPDLSCs were investigated through its inhibition or overexpression. Expression of the sex-determining region Y-related HMG-box 11 (SOX11) and osteogenic markers was analyzed using Western blot and real-time PCR. Osteogenesis was measured using alizarin red S (ARS) staining and alkaline phosphatase (ALP) staining. A dual luciferase reporter assay was performed to confirm SOX11 as a target of miR-508-5p. Results During the osteogenic differentiation of hPDLSCs, miR-508-5p expression level gradually decreased, while that of SOX11 increased. miR-508-5p inhibition significantly promoted osteogenesis in hPDLSCs, while overexpression inhibited the process. SOX11 overexpression reversed the suppressive effects of miR-508-5p on the osteogenic differentiation of hPDLSCs. miR-508-5p downregulation significantly increased SOX11; a dual luciferase reporter assay provided evidence for their direct targeting. Conclusion miR-508-5p downregulation promotes the osteogenic differentiation of hPDLSCs by targeting SOX11.
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Affiliation(s)
- Jing Guo
- Department of Periodontology, Peking University School and Hospital of Stomatology & National Clinical Research Center for Oral Diseases & National Engineering Laboratory for Digital and Material Technology of Stomatology & Beijing Key Laboratory of Digital Stomatology & Research Center of Engineering and Technology for Computerized Dentisitry Minisrty of Health, Beijing, China
| | - Xiang-Ying Ouyang
- Department of Periodontology, Peking University School and Hospital of Stomatology & National Clinical Research Center for Oral Diseases & National Engineering Laboratory for Digital and Material Technology of Stomatology & Beijing Key Laboratory of Digital Stomatology & Research Center of Engineering and Technology for Computerized Dentisitry Minisrty of Health, Beijing, China
| | - Jian-Ru Liu
- Department of Periodontology, Peking University School and Hospital of Stomatology & National Clinical Research Center for Oral Diseases & National Engineering Laboratory for Digital and Material Technology of Stomatology & Beijing Key Laboratory of Digital Stomatology & Research Center of Engineering and Technology for Computerized Dentisitry Minisrty of Health, Beijing, China
| | - Wen-Yi Liu
- Department of Periodontology, Peking University School and Hospital of Stomatology & National Clinical Research Center for Oral Diseases & National Engineering Laboratory for Digital and Material Technology of Stomatology & Beijing Key Laboratory of Digital Stomatology & Research Center of Engineering and Technology for Computerized Dentisitry Minisrty of Health, Beijing, China
| | - Yuan-Bo Wang
- Department of Periodontology, Peking University School and Hospital of Stomatology & National Clinical Research Center for Oral Diseases & National Engineering Laboratory for Digital and Material Technology of Stomatology & Beijing Key Laboratory of Digital Stomatology & Research Center of Engineering and Technology for Computerized Dentisitry Minisrty of Health, Beijing, China
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Zhou H, Xiang R, Chen W, Peng Y, Chen Z, Chen W, Tang L. CircRNA-mediated heterogeneous ceRNA regulation mechanism in periodontitis and peri-implantitis. Eur J Med Res 2024; 29:594. [PMID: 39695789 DOI: 10.1186/s40001-024-02153-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/14/2024] [Accepted: 11/11/2024] [Indexed: 12/20/2024] Open
Abstract
BACKGROUND Performing a comprehensive study on the differential expression of mRNAs, miRNAs, and circRNAs in the context of peri-implantitis and periodontitis has beneficial advantages to identify unique molecular signatures and pathways that may contribute to our understanding of these conditions. METHODS Gingival tissues from healthy individuals and peri-implantitis and periodontitis patients were obtained to identify differential expression genes (DEG) by Illumina HiSeq 2500 instrument. Differential expression analysis was conducted using R statistical software, with significance set at P < 0.05 and fold greater than 2. Functional enrichment analysis of the DEGs was conducted using the Reactome, Gene ontology and KEGG databases. RESULTS Significant differences in mRNA, miRNA, and circRNA profiles were identified between healthy gingival tissues. The top DEGs comprising 6 circRNAs, 2 miRNAs, and 4 mRNAs were identified and the constructed ceRNA network, elucidates their involvement in key signaling pathways such as ErbB, Wnt, and mTOR, which are crucial for understanding the inflammatory progression of these conditions. CONCLUSIONS This study highlights a heterogeneous circRNA-mediated ceRNA regulatory mechanism in peri-implantitis and periodontitis, activating signaling pathways and regulating gene expression. Key findings including a detailed analysis of the transcriptional landscape and identification of unique molecular signatures, pathways and cellular components in gingival tissues, offering insights into the molecular differences between peri-implantitis and periodontitis. The study may contribute to the understanding of the pathological mechanisms of these diseases and may aid in the development of targeted therapies.
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Affiliation(s)
- Hailun Zhou
- Guangxi Medical University, Nanning, 530021, China
- Guangxi Key Laboratory of the Rehabilitation and Reconstruction of Oral and Maxillofacial Research, Nanning, 530021, China
- Guangxi Health Commission Key Laboratory of Prevention and Treatment for Oral Infectious Diseases, Nanning, 530021, China
- Guangxi Clinical Research Center for Craniofacial Deformity, Nanning, 530021, China
| | - Rong Xiang
- Guangxi Medical University, Nanning, 530021, China
- Guangxi Key Laboratory of the Rehabilitation and Reconstruction of Oral and Maxillofacial Research, Nanning, 530021, China
- Guangxi Health Commission Key Laboratory of Prevention and Treatment for Oral Infectious Diseases, Nanning, 530021, China
- Guangxi Clinical Research Center for Craniofacial Deformity, Nanning, 530021, China
| | - Wenjin Chen
- Guangxi Medical University, Nanning, 530021, China
- Guangxi Key Laboratory of the Rehabilitation and Reconstruction of Oral and Maxillofacial Research, Nanning, 530021, China
- Guangxi Health Commission Key Laboratory of Prevention and Treatment for Oral Infectious Diseases, Nanning, 530021, China
- Guangxi Clinical Research Center for Craniofacial Deformity, Nanning, 530021, China
| | - Yuanyuan Peng
- Guangxi Medical University, Nanning, 530021, China
- Guangxi Key Laboratory of the Rehabilitation and Reconstruction of Oral and Maxillofacial Research, Nanning, 530021, China
- Guangxi Health Commission Key Laboratory of Prevention and Treatment for Oral Infectious Diseases, Nanning, 530021, China
- Guangxi Clinical Research Center for Craniofacial Deformity, Nanning, 530021, China
| | - Zhiyong Chen
- Guangxi Medical University, Nanning, 530021, China
- Guangxi Key Laboratory of the Rehabilitation and Reconstruction of Oral and Maxillofacial Research, Nanning, 530021, China
- Guangxi Health Commission Key Laboratory of Prevention and Treatment for Oral Infectious Diseases, Nanning, 530021, China
- Guangxi Clinical Research Center for Craniofacial Deformity, Nanning, 530021, China
| | - Wenxia Chen
- Guangxi Medical University, Nanning, 530021, China.
- Guangxi Key Laboratory of the Rehabilitation and Reconstruction of Oral and Maxillofacial Research, Nanning, 530021, China.
- Guangxi Health Commission Key Laboratory of Prevention and Treatment for Oral Infectious Diseases, Nanning, 530021, China.
- Guangxi Clinical Research Center for Craniofacial Deformity, Nanning, 530021, China.
- Department of Endodontics Dentistry, College of Stomatology, Guangxi Medical University, Nanning, 530021, China.
| | - Li Tang
- Guangxi Medical University, Nanning, 530021, China.
- Guangxi Key Laboratory of the Rehabilitation and Reconstruction of Oral and Maxillofacial Research, Nanning, 530021, China.
- Guangxi Health Commission Key Laboratory of Prevention and Treatment for Oral Infectious Diseases, Nanning, 530021, China.
- Guangxi Clinical Research Center for Craniofacial Deformity, Nanning, 530021, China.
- Department of Implant Dentistry, College of Stomatology, Guangxi Medical University, Nanning, 530021, China.
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Arumuganainar D, Yadalam PK, Ardila CM. Artificial Intelligence-Enhanced Exosomal-Derived MicroRNA From Developing Teeth. Int Dent J 2024; 74:1178-1179. [PMID: 39030095 PMCID: PMC11561507 DOI: 10.1016/j.identj.2024.06.018] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/12/2024] [Revised: 06/14/2024] [Accepted: 06/17/2024] [Indexed: 07/21/2024] Open
Affiliation(s)
- Deepavalli Arumuganainar
- Department of Periodontics, Saveetha Dental College and Hospital, Saveetha Institute of Medical and Technical Sciences, SIMATS, Saveetha University, Chennai, Tamil Nadu, India
| | - Pradeep Kumar Yadalam
- Department of Periodontics, Saveetha Dental College and Hospital, Saveetha Institute of Medical and Technical Sciences, SIMATS, Saveetha University, Chennai, Tamil Nadu, India.
| | - Carlos M Ardila
- Biomedical Stomatology Research Group, Universidad de Antioquia U de A, Medellín, Colombia.
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Li J, Wang S, Ren Y, Li H, Zhou Y, Lan X, Wang Y. Differential expression of circRNAs during osteogenic/odontogenic differentiation of stem cells from apical papilla promoted by blue light-emitting diode. Mol Biol Rep 2024; 51:710. [PMID: 38824241 DOI: 10.1007/s11033-024-09621-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/03/2024] [Accepted: 05/07/2024] [Indexed: 06/03/2024]
Abstract
BACKGROUND Circular RNA (circRNA) is a key player in regulating the multidirectional differentiation of stem cells. Previous research by our group found that the blue light-emitting diode (LED) had a promoting effect on the osteogenic/odontogenic differentiation of human stem cells from apical papilla (SCAPs). This research aimed to investigate the differential expression of circRNAs during the osteogenic/odontogenic differentiation of SCAPs regulated by blue LED. MATERIALS AND METHODS SCAPs were divided into the irradiation group (4 J/cm2) and the control group (0 J/cm2), and cultivated in an osteogenic/odontogenic environment. The differentially expressed circRNAs during osteogenic/odontogenic differentiation of SCAPs promoted by blue LED were detected by high-throughput sequencing, and preliminarily verified by qRT-PCR. Functional prediction of these circRNAs was performed using Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) and the circRNA-miRNA-mRNA networks were also constructed. RESULTS It showed 301 circRNAs were differentially expressed. GO and KEGG analyses suggested that these circRNAs were associated with some signaling pathways related to osteogenic/odontogenic differentiation. And the circRNA-miRNA-mRNA networks were also successfully constructed. CONCLUSION CircRNAs were involved in the osteogenic/odontogenic differentiation of SCAPs promoted by blue LED. In this biological process, circRNA-miRNA-mRNA networks served an important purpose, and circRNAs regulated this process through certain signaling pathways.
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Affiliation(s)
- Jiaxin Li
- School of Stomatology, Southwest Medical University, Luzhou, 646000, China
- The Department of Preventive Dentistry, The Affiliated Stomatological Hospital, Southwest Medical University, Luzhou, 646000, China
- Luzhou Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Southwest Medical University, Luzhou, 646000, China
- Institute of Stomatology, Southwest Medical University, Luzhou, 646000, China
| | - Shifen Wang
- School of Stomatology, Southwest Medical University, Luzhou, 646000, China
- The Department of Preventive Dentistry, The Affiliated Stomatological Hospital, Southwest Medical University, Luzhou, 646000, China
- Luzhou Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Southwest Medical University, Luzhou, 646000, China
- Institute of Stomatology, Southwest Medical University, Luzhou, 646000, China
| | - Yajiao Ren
- School of Stomatology, Southwest Medical University, Luzhou, 646000, China
- The Department of Preventive Dentistry, The Affiliated Stomatological Hospital, Southwest Medical University, Luzhou, 646000, China
- Luzhou Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Southwest Medical University, Luzhou, 646000, China
- Institute of Stomatology, Southwest Medical University, Luzhou, 646000, China
| | - Hao Li
- School of Stomatology, Southwest Medical University, Luzhou, 646000, China
- The Department of Preventive Dentistry, The Affiliated Stomatological Hospital, Southwest Medical University, Luzhou, 646000, China
- Luzhou Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Southwest Medical University, Luzhou, 646000, China
- Institute of Stomatology, Southwest Medical University, Luzhou, 646000, China
| | - Yan Zhou
- School of Stomatology, Southwest Medical University, Luzhou, 646000, China
- The Department of Preventive Dentistry, The Affiliated Stomatological Hospital, Southwest Medical University, Luzhou, 646000, China
- Luzhou Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Southwest Medical University, Luzhou, 646000, China
- Institute of Stomatology, Southwest Medical University, Luzhou, 646000, China
| | - Xiaorong Lan
- Luzhou Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Southwest Medical University, Luzhou, 646000, China
| | - Yao Wang
- School of Stomatology, Southwest Medical University, Luzhou, 646000, China.
- The Department of Preventive Dentistry, The Affiliated Stomatological Hospital, Southwest Medical University, Luzhou, 646000, China.
- Luzhou Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Southwest Medical University, Luzhou, 646000, China.
- Institute of Stomatology, Southwest Medical University, Luzhou, 646000, China.
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Liu J, Liu R, Wang H, Zhang Z, Wang J, Wei F. CircPRKD3/miR-6783-3p responds to mechanical force to facilitate the osteogenesis of stretched periodontal ligament stem cells. J Orthop Surg Res 2024; 19:257. [PMID: 38649946 PMCID: PMC11036753 DOI: 10.1186/s13018-024-04727-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/11/2024] [Accepted: 04/06/2024] [Indexed: 04/25/2024] Open
Abstract
BACKGROUND The mechanotransduction mechanisms by which cells regulate tissue remodeling are not fully deciphered. Circular RNAs (circRNAs) are crucial to various physiological processes, including cell cycle, differentiation, and polarization. However, the effects of mechanical force on circRNAs and the role of circRNAs in the mechanobiology of differentiation and remodeling in stretched periodontal ligament stem cells (PDLSCs) remain unclear. This article aims to explore the osteogenic function of mechanically sensitive circular RNA protein kinase D3 (circPRKD3) and elucidate its underlying mechanotransduction mechanism. MATERIALS AND METHODS PDLSCs were elongated with 8% stretch at 0.5 Hz for 24 h using the Flexcell® FX-6000™ Tension System. CircPRKD3 was knockdown or overexpressed with lentiviral constructs or plasmids. The downstream molecules of circPRKD3 were predicted by bioinformatics analysis. The osteogenic effect of related molecules was evaluated by quantitative real-time PCR (qRT-PCR) and western blot. RESULTS Mechanical force enhanced the osteogenesis of PDLSCs and increased the expression of circPRKD3. Knockdown of circPRKD3 hindered PDLSCs from osteogenesis under mechanical force, while overexpression of circPRKD3 promoted the early osteogenesis process of PDLSCs. With bioinformatics analysis and multiple software predictions, we identified hsa-miR-6783-3p could act as the sponge of circPRKD3 to indirectly regulate osteogenic differentiation of mechanically stimulated PDLSCs. CONCLUSIONS Our results first suggested that both circPRKD3 and hsa-miR-6783-3p could enhance osteogenesis of stretched PDLSCs. Furthermore, hsa-miR-6783-3p could sponge circPRKD3 to indirectly regulate RUNX2 during the periodontal tissue remodeling process in orthodontic treatment.
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Affiliation(s)
- Jiani Liu
- Department of Orthodontics, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University & Shandong Key Laboratory of Oral Tissue Regeneration & Shandong Engineering Research Center of Dental Materials and Oral Tissue Regeneration & Shandong Provincial Clinical Research Center for Oral Diseases, No. 44-1 Wenhua Road West, Jinan, Shandong, 250012, China
| | - Rui Liu
- Department of Orthodontics, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University & Shandong Key Laboratory of Oral Tissue Regeneration & Shandong Engineering Research Center of Dental Materials and Oral Tissue Regeneration & Shandong Provincial Clinical Research Center for Oral Diseases, No. 44-1 Wenhua Road West, Jinan, Shandong, 250012, China
| | - Hong Wang
- Department of Orthodontics, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University & Shandong Key Laboratory of Oral Tissue Regeneration & Shandong Engineering Research Center of Dental Materials and Oral Tissue Regeneration & Shandong Provincial Clinical Research Center for Oral Diseases, No. 44-1 Wenhua Road West, Jinan, Shandong, 250012, China
| | - Zijie Zhang
- Department of Orthodontics, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University & Shandong Key Laboratory of Oral Tissue Regeneration & Shandong Engineering Research Center of Dental Materials and Oral Tissue Regeneration & Shandong Provincial Clinical Research Center for Oral Diseases, No. 44-1 Wenhua Road West, Jinan, Shandong, 250012, China
| | - Jixiao Wang
- Department of Orthodontics, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University & Shandong Key Laboratory of Oral Tissue Regeneration & Shandong Engineering Research Center of Dental Materials and Oral Tissue Regeneration & Shandong Provincial Clinical Research Center for Oral Diseases, No. 44-1 Wenhua Road West, Jinan, Shandong, 250012, China
| | - Fulan Wei
- Department of Orthodontics, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University & Shandong Key Laboratory of Oral Tissue Regeneration & Shandong Engineering Research Center of Dental Materials and Oral Tissue Regeneration & Shandong Provincial Clinical Research Center for Oral Diseases, No. 44-1 Wenhua Road West, Jinan, Shandong, 250012, China.
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Wang Q, Yang X, Wang X, Wang X, Zhang J, Gao Y, Pan J, Wang S. Identifying genes for regulating osteogenic differentiation of human periodontal ligament stem cells in inflammatory environments by bioinformatics analysis. J Periodontal Res 2024; 59:311-324. [PMID: 38082497 DOI: 10.1111/jre.13215] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/23/2023] [Revised: 10/03/2023] [Accepted: 11/15/2023] [Indexed: 03/23/2024]
Abstract
BACKGROUND AND OBJECTIVES Periodontitis is an immuno-inflammatory disease caused by dental plaque biofilms and inflammations. The regeneration of bone tissue in inflammatory environment is of great significance for the treatment of periodontal disease, but the specific molecular mechanism of bone formation in periodontitis still needs further exploration. The objective of this study was to identify key osteogenesis-related genes (ORGs) in periodontitis. METHODS We used two datasets from the Gene Expression Omnibus (GEO) database to find differentially expressed mRNAs and miRNAs, further performed Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. Then we predicted the downstream genes of the differentially expressed miRNAs (DEMs) by the TargetScan database and established a miRNA-mRNA regulatory network. Finally, the osteogenic mechanism of periodontitis was explored through quantitative real-time PCR (qRT-PCR) by inducing inflammatory environment and osteogenic differentiation of hPDLSCs. RESULTS Through differential expression analysis and prediction of downstream target genes of DEMs, we created a miRNA-mRNA regulatory network consisting of 29 DEMs and 11 differentially expressed osteogenesis-related genes (DEORGs). In addition, the qRT-PCR results demonstrated that BTBD3, PLAT, AKAP12, SGK1, and GLCE expression levels were significantly upregulated, while those of TIMP3, ZCCHC14, LIN7A, DNAH6, NNT, and ITGA6 were downregulated under the dual effects of inflammatory stimulation and osteogenic induction. CONCLUSION DEORGs might be important factors in the osteogenic phase of periodontitis, and the miRNA-mRNA network may shed light on the clarification of the role and mechanism of osteogenesis in periodontitis and contribute to the development of novel therapeutic strategies.
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Affiliation(s)
- Qing Wang
- Department of stomatology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Xiaojie Yang
- Department of stomatology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Xuechun Wang
- Department of stomatology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Xuan Wang
- Department of stomatology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Jie Zhang
- Department of stomatology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Ya Gao
- Department of stomatology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Jinsong Pan
- Department of stomatology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Shiwei Wang
- Department of stomatology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
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10
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Suciu TS, Feștilă D, Berindan-Neagoe I, Nutu A, Armencea G, Aghiorghiesei AI, Vulcan T, Băciuț M. Circular RNA-Mediated Regulation of Oral Tissue-Derived Stem Cell Differentiation: Implications for Oral Medicine and Orthodontic Applications. Stem Cell Rev Rep 2024; 20:656-671. [PMID: 38279054 PMCID: PMC10984898 DOI: 10.1007/s12015-024-10683-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 01/16/2024] [Indexed: 01/28/2024]
Abstract
Circular RNAs (circRNAs) are a novel class of endogenous non-coding RNAs (ncRNAs) which unlike linear RNAs, have a covalently closed continuous loop structure. circRNAs are found abundantly in human cells and their biology is complex. They feature unique expression to different types of cells, tissues, and developmental stages. To the present, the functional roles of circular RNAs are not fully understood. They reportedly act as microRNA (miRNA) sponges, therefore having key regulatory functions in diverse physiological and pathological processes. As for dentistry field, lines of evidence indicate that circRNAs play vital roles in the odontogenic and osteogenic differentiation of dental pulp stem cells (DPSCs) and periodontal ligament stem cells (PDLSCs). Abnormal expression of circRNAs have been found in other areas of pathology frequently reflected also in the oral environment, such as inflammation or bone and soft tissue loss. Therefore, circRNAs could be of significant importance in various fields in dentistry, especially in bone and soft tissue engineering and regeneration. Understanding the molecular mechanisms occurring during the regulation of oral biological and tissue remodeling processes could augment the discovery of novel diagnostic biomarkers and therapeutic strategies that will improve orthodontic and other oral therapeutic protocols.
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Affiliation(s)
- Tudor-Sergiu Suciu
- Department of Orthodontics and Dentofacial Orthopedics, Iuliu Hațieganu University of Medicine and Pharmacy, 400083, Cluj-Napoca, Romania
| | - Dana Feștilă
- Department of Orthodontics and Dentofacial Orthopedics, Iuliu Hațieganu University of Medicine and Pharmacy, 400083, Cluj-Napoca, Romania.
| | - Ioana Berindan-Neagoe
- Research Center for Functional Genomics, Biomedicine and Translational Medicine, Iuliu Hațieganu University of Medicine and Pharmacy, 400337, Cluj-Napoca, Romania
| | - Andreea Nutu
- Research Center for Functional Genomics, Biomedicine and Translational Medicine, Iuliu Hațieganu University of Medicine and Pharmacy, 400337, Cluj-Napoca, Romania
| | - Gabriel Armencea
- Department of Maxillofacial Surgery and Implantology, Iuliu Hațieganu University of Medicine and Pharmacy, 400029, Cluj-Napoca, Romania
| | - Alexandra Iulia Aghiorghiesei
- Department of Prosthodontics and Dental Materials, Iuliu Hațieganu University of Medicine and Pharmacy, 400006, Cluj-Napoca, Romania
| | - Talida Vulcan
- Department of Dermatology, Iuliu Hațieganu University of Medicine and Pharmacy, 400006, Cluj-Napoca, Romania
| | - Mihaela Băciuț
- Department of Maxillofacial Surgery and Implantology, Iuliu Hațieganu University of Medicine and Pharmacy, 400029, Cluj-Napoca, Romania
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11
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Zhu Y, Guan X, Geng X, Du Y, Jin S, Liu J. The signaling pathways involved in non-coding RNA regulation during osteogenic differentiation of periodontal tissue-derived cells in the field of periodontitis. J Periodontal Res 2024; 59:18-31. [PMID: 37961979 DOI: 10.1111/jre.13199] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/16/2023] [Revised: 09/07/2023] [Accepted: 10/12/2023] [Indexed: 11/15/2023]
Abstract
Periodontitis is a prevalent oral disease caused by chronic inflammation of the periodontal tissues surrounding the teeth, which can lead to bone loss, tooth loosening, and even tooth loss. This inflammation has a negative impact on the osteogenic differentiation capacity of periodontal tissue-derived cells. Non-coding RNAs (ncRNAs) are a class of RNA molecules that do not encode proteins but can regulate various physiological processes. In this review, we summarized the critical signaling pathways that ncRNAs modulate in osteogenic differentiation of periodontal tissue-derived cells, such as the Wnt, BMP/Smad, NF-κB, and PI3-K/Akt/mTOR pathways. This comprehensive exploration of ncRNA-mediated modulation offers fresh and promising insights for prospective approaches in the management of periodontitis and the advancement of periodontal regeneration therapies.
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Affiliation(s)
- Yinci Zhu
- School of Stomatology, Zunyi Medical University, Zunyi, China
| | - Xiaoyan Guan
- Department of Orthodontics, Affiliated Stomatological Hospital of Zunyi Medical University, Zunyi, China
| | - Xiaorui Geng
- Department of Otolaryngology. Longgang E.N.T Hospital & Shenzhen Key Laboratory of E.N.T, Institute of E.N.T Shenzhen, Shenzhen, China
| | - Yuanhang Du
- School of Stomatology, Zunyi Medical University, Zunyi, China
| | - Suhan Jin
- Department of Orthodontics, Affiliated Stomatological Hospital of Zunyi Medical University, Zunyi, China
| | - Jianguo Liu
- School of Stomatology, Zunyi Medical University, Zunyi, China
- Special Key Laboratory of Oral Diseases Research, Higher Education Institution, Zunyi, China
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12
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Baniasadi M, Talebi S, Mokhtari K, Zabolian AH, Khosroshahi EM, Entezari M, Dehkhoda F, Nabavi N, Hashemi M. Role of non-coding RNAs in osteoporosis. Pathol Res Pract 2024; 253:155036. [PMID: 38134836 DOI: 10.1016/j.prp.2023.155036] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/29/2023] [Revised: 12/10/2023] [Accepted: 12/10/2023] [Indexed: 12/24/2023]
Abstract
Osteoporosis, a prevalent bone disorder influenced by genetic and environmental elements, significantly increases the likelihood of fractures and bone weakness, greatly affecting the lives of those afflicted. Yet, the exact epigenetic processes behind the onset of osteoporosis are still unclear. Growing research indicates that epigenetic changes could act as vital mediators that connect genetic tendencies and environmental influences, thereby increasing the risk of osteoporosis and bone fractures. Within these epigenetic factors, certain types of RNA, such as microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs), have been recognized as key regulatory elements. These RNA types wield significant influence on gene expression through epigenetic regulation, directing various biological functions essential to bone metabolism. This extensive review compiles current research uncovering the complex ways in which miRNAs, lncRNAs, and circRNAs are involved in the development of osteoporosis, especially in osteoblasts and osteoclasts. Gaining a more profound understanding of the roles these three RNA classes play in osteoporosis could reveal new diagnostic methods and treatment approaches for this incapacitating condition. In conclusion, this review delves into the complex domain of epigenetic regulation via non-coding RNA in osteoporosis. It sheds light on the complex interactions and mechanisms involving miRNAs, lncRNAs, and circRNAs within osteoblasts and osteoclasts, offering an in-depth understanding of the less explored aspects of osteoporosis pathogenesis. These insights not only reveal the complexity of the disease but also offer significant potential for developing new diagnostic methods and targeted treatments. Therefore, this review marks a crucial step in deciphering the elusive complexities of osteoporosis, leading towards improved patient care and enhanced quality of life.
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Affiliation(s)
- Mojtaba Baniasadi
- Department of Orthopedics, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Sina Talebi
- Department of Orthopedics, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Khatere Mokhtari
- Department of Cellular and Molecular Biology and Microbiology, Faculty of Biological Science and Technology, University of Isfahan, Isfahan, Iran; Department of Animal Biotechnology, Cell Science Research Center, Royan Institute for Biotechnology, ACECR, Isfahan,Iran
| | - Amir Hossein Zabolian
- Department of Orthopedics, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Elahe Mohandesi Khosroshahi
- Farhikhtegan Medical Convergence Sciences Research Center, Farhikhtegan Hospital Tehran Medical Sciences, Islamic Azad University, Tehran, Iran; Department of Genetics, Faculty of Advanced Science and Technology, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran
| | - Maliheh Entezari
- Farhikhtegan Medical Convergence Sciences Research Center, Farhikhtegan Hospital Tehran Medical Sciences, Islamic Azad University, Tehran, Iran; Department of Genetics, Faculty of Advanced Science and Technology, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran.
| | - Farshid Dehkhoda
- Department of Orthopedics, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
| | - Noushin Nabavi
- Department of Urologic Sciences, University of British Columbia, Vancouver, BC V5Z 1M9, Canada
| | - Mehrdad Hashemi
- Farhikhtegan Medical Convergence Sciences Research Center, Farhikhtegan Hospital Tehran Medical Sciences, Islamic Azad University, Tehran, Iran; Department of Genetics, Faculty of Advanced Science and Technology, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran.
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13
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Hu G, Wu L, Xue K, Han H, Sun Y, Gan K, Zhu J, Shi Q, Du T. Differential expression of circular RNAs in interleukin 6-promoted osteogenic differentiation of human stem cells from apical papilla. Clin Oral Investig 2023; 27:7765-7776. [PMID: 37962668 DOI: 10.1007/s00784-023-05366-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/07/2023] [Accepted: 10/25/2023] [Indexed: 11/15/2023]
Abstract
INTRODUCTION Studies have shown that interleukin 6 (IL-6) can regulate stem cell osteogenic differentiation; however, the exact mechanism is not clear. Circular RNAs (circRNAs) are closed circular non-coding RNAs that are involved in the process of stem cell osteogenic differentiation. Therefore, the purpose of this present study was to investigate the effect of IL-6 treatment on osteogenic differentiation of human apical tooth papillae stem cells (hSCAPs), and to detect the difference in circRNA expression using gene microarray technology. METHODS After extraction and identification of hSCAPs, alkaline phosphatase (ALP) activity, alizarin red staining, and calcium ion quantitative assay were used to determine the changes of ALP enzyme, mineralized nodules, and matrix calcium levels before and after IL-6 treatment of hSCAPs gene microarray technology was used to analyze the changes in circRNA expression levels before and after IL-6 induction of mineralization. The four selected circRNAs were validated by qRT-PCR. Moreover, gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) were used to predict the potential functions and biological signaling pathways of circRNAs. Finally, these data are integrated and analyzed to construct circRNA-microRNA-mRNA networks. RESULTS Alp and Alizarin red staining confirmed that IL-6 promoted the osteogenic differentiation of hSCAPs. The gene microarray results identified 132 differentially expressed circRNAs, of which 117 were upregulated and 15 were downregulated. Bioinformatic analysis predicted that the circRNA-406620/miR-103a-3p/FAT atypical cadherin 4 (FAT4) pathway might be involved in regulating IL-6 to promote osteogenic differentiation of hSCAPs. CONCLUSION Differentially expressed circRNAs might be closely involved in regulating IL-6 to promote osteogenic differentiation of hSCAPs.
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Affiliation(s)
- Guang Hu
- Department of Stomatology, The First Affiliated Hospital of Zhengzhou University, No.1 Jianshe East Road, Zhengzhou, 450052, Henan, China
| | - Laidi Wu
- Department of Stomatology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China
- School of Stomatology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China
| | - Kaiyang Xue
- Department of Stomatology, The First Affiliated Hospital of Zhengzhou University, No.1 Jianshe East Road, Zhengzhou, 450052, Henan, China
| | - Hao Han
- Department of Stomatology, The First Affiliated Hospital of Zhengzhou University, No.1 Jianshe East Road, Zhengzhou, 450052, Henan, China
| | - Yuhui Sun
- Department of Stomatology, The First Affiliated Hospital of Zhengzhou University, No.1 Jianshe East Road, Zhengzhou, 450052, Henan, China
| | - Kang Gan
- Department of Stomatology, The First Affiliated Hospital of Zhengzhou University, No.1 Jianshe East Road, Zhengzhou, 450052, Henan, China
| | - Juanfang Zhu
- Department of Stomatology, The First Affiliated Hospital of Zhengzhou University, No.1 Jianshe East Road, Zhengzhou, 450052, Henan, China
| | - Qi Shi
- Department of Stomatology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
- School of Stomatology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
| | - Tianfeng Du
- Department of Stomatology, The First Affiliated Hospital of Zhengzhou University, No.1 Jianshe East Road, Zhengzhou, 450052, Henan, China.
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14
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Wang S, Pan C, Sheng H, Yang M, Yang C, Feng X, Hu C, Ma Y. Construction of a molecular regulatory network related to fat deposition by multi-tissue transcriptome sequencing of Jiaxian red cattle. iScience 2023; 26:108346. [PMID: 38026203 PMCID: PMC10665818 DOI: 10.1016/j.isci.2023.108346] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/02/2023] [Revised: 09/26/2023] [Accepted: 10/23/2023] [Indexed: 12/01/2023] Open
Abstract
Intramuscular fat (IMF) refers to the fat that accumulates between muscle bundles or within muscle cells, whose content significantly impacts the taste, tenderness, and flavor of meat products, making it a crucial economic characteristic in livestock production. However, the intricate mechanisms governing IMF deposition, involving non-coding RNAs (ncRNAs), genes, and complex regulatory networks, remain largely enigmatic. Identifying adipose tissue-specific genes and ncRNAs is paramount to unravel these molecular mysteries. This study, conducted on Jiaxian red cattle, harnessed whole transcriptome sequencing to unearth the nuances of circRNAs and miRNAs across seven distinct tissues. The interplay of these ncRNAs was assessed through differential expression analysis and network analysis. These findings are not only pivotal in unveiling the intricacies of fat deposition mechanisms but also lay a robust foundation for future research, setting the stage for enhancing IMF content in Jiaxian red cattle breeding.
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Affiliation(s)
- Shuzhe Wang
- Key Laboratory of Ruminant Molecular and Cellular Breeding of Ningxia Hui Autonomous Region, College of Animal Science and Technology, Ningxia University, Yinchuan 750021, China
| | - Cuili Pan
- Key Laboratory of Ruminant Molecular and Cellular Breeding of Ningxia Hui Autonomous Region, College of Animal Science and Technology, Ningxia University, Yinchuan 750021, China
| | - Hui Sheng
- Key Laboratory of Ruminant Molecular and Cellular Breeding of Ningxia Hui Autonomous Region, College of Animal Science and Technology, Ningxia University, Yinchuan 750021, China
| | - Mengli Yang
- Key Laboratory of Ruminant Molecular and Cellular Breeding of Ningxia Hui Autonomous Region, College of Animal Science and Technology, Ningxia University, Yinchuan 750021, China
| | - Chaoyun Yang
- Xichang College, Liangshan Prefecture, Sichuan Province, China
| | - Xue Feng
- Key Laboratory of Ruminant Molecular and Cellular Breeding of Ningxia Hui Autonomous Region, College of Animal Science and Technology, Ningxia University, Yinchuan 750021, China
| | - Chunli Hu
- Key Laboratory of Ruminant Molecular and Cellular Breeding of Ningxia Hui Autonomous Region, College of Animal Science and Technology, Ningxia University, Yinchuan 750021, China
| | - Yun Ma
- Key Laboratory of Ruminant Molecular and Cellular Breeding of Ningxia Hui Autonomous Region, College of Animal Science and Technology, Ningxia University, Yinchuan 750021, China
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15
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Zhang L, Sheng M, Cao H, Zhang L, Shao W. Decoding the role of long non-coding RNAs in periodontitis: A comprehensive review. Biomed Pharmacother 2023; 166:115357. [PMID: 37619483 DOI: 10.1016/j.biopha.2023.115357] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/15/2023] [Revised: 08/13/2023] [Accepted: 08/21/2023] [Indexed: 08/26/2023] Open
Abstract
Periodontitis is an inflammatory disease characterized by the pathological loss of alveolar bone and the adjacent periodontal ligament. It is considered a disease that imposes a substantial health burden, with an incidence rate of 20-50%. The etiology of periodontitis is multifactorial, with genetic factors accounting for approximately half of severe cases. Studies have revealed that long non-coding RNAs (lncRNAs) play a pivotal role in periodontitis pathogenesis. Accumulating evidence suggests that lncRNAs have distinct regulatory mechanisms, enabling them to control numerous vital processes in periodontal cells, including osteogenic differentiation, inflammation, proliferation, apoptosis, and autophagy. In this review, we summarize the diverse roles of lncRNAs in the pathogenesis of periodontitis, shedding light on the underlying mechanisms of disease development. By highlighting the potential of lncRNAs as biomarkers and therapeutic targets, this review offers a new perspective on the diagnosis and treatment of periodontitis, paving the way for further investigation into the field of lncRNA-based therapeutics.
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Affiliation(s)
- Lizhi Zhang
- College & Hospital of Stomatology, Anhui Medical University, Key Lab. of Oral Diseases Research of Anhui Province, Hefei 230032, China; First Clinical Medical College, Anhui Medical University, Hefei, China
| | - Mengfei Sheng
- Department of Microbiology and Parasitology, Anhui Provincial Laboratory of Pathogen Biology, School of Basic Medical Sciences, Anhui Medical University, Hefei 230032, Anhui, China
| | - Huake Cao
- First Clinical Medical College, Anhui Medical University, Hefei, China
| | - Lei Zhang
- College & Hospital of Stomatology, Anhui Medical University, Key Lab. of Oral Diseases Research of Anhui Province, Hefei 230032, China.
| | - Wei Shao
- College & Hospital of Stomatology, Anhui Medical University, Key Lab. of Oral Diseases Research of Anhui Province, Hefei 230032, China; Department of Microbiology and Parasitology, Anhui Provincial Laboratory of Pathogen Biology, School of Basic Medical Sciences, Anhui Medical University, Hefei 230032, Anhui, China.
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16
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Eun JW, Cheong JY, Jeong JY, Kim HS. A New Understanding of Long Non-Coding RNA in Hepatocellular Carcinoma-From m 6A Modification to Blood Biomarkers. Cells 2023; 12:2272. [PMID: 37759495 PMCID: PMC10528438 DOI: 10.3390/cells12182272] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/21/2023] [Revised: 09/12/2023] [Accepted: 09/13/2023] [Indexed: 09/29/2023] Open
Abstract
With recent advancements in biological research, long non-coding RNAs (lncRNAs) with lengths exceeding 200 nucleotides have emerged as pivotal regulators of gene expression and cellular phenotypic modulation. Despite initial skepticism due to their low sequence conservation and expression levels, their significance in various biological processes has become increasingly apparent. We provided an overview of lncRNAs and discussed their defining features and modes of operation. We then explored their crucial function in the hepatocarcinogenesis process, elucidating their complex involvement in hepatocellular carcinoma (HCC). The influential role of lncRNAs within the HCC tumor microenvironment is emphasized, illustrating their potential as key modulators of disease dynamics. We also investigated the significant influence of N6-methyladenosine (m6A) modification on lncRNA function in HCC, enhancing our understanding of both their roles and their upstream regulators. Additionally, the potential of lncRNAs as promising biomarkers was discussed in liver cancer diagnosis, suggesting a novel avenue for future research and clinical application. Finally, our work underscored the dual potential of lncRNAs as both contributors to HCC pathogenesis and innovative tools for its diagnosis. Existing challenges and prospective trajectories in lncRNA research are also discussed, emphasizing their potential in advancing liver cancer research.
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Affiliation(s)
- Jung Woo Eun
- Department of Gastroenterology, Ajou University School of Medicine, 164 World cup-ro, Yeongtong-gu, Suwon 16499, Republic of Korea; (J.W.E.); (J.Y.C.)
| | - Jae Youn Cheong
- Department of Gastroenterology, Ajou University School of Medicine, 164 World cup-ro, Yeongtong-gu, Suwon 16499, Republic of Korea; (J.W.E.); (J.Y.C.)
| | - Jee-Yeong Jeong
- Department of Biochemistry, College of Medicine, Kosin University, Seo-gu, Busan 49267, Republic of Korea;
- Institute for Medical Science, College of Medicine, Kosin University, Seo-gu, Busan 49267, Republic of Korea
| | - Hyung Seok Kim
- Department of Biochemistry, College of Medicine, Kosin University, Seo-gu, Busan 49267, Republic of Korea;
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17
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Wang W, Chen B, Yang J, Li Y, Ding H, Liu H, Yuan C. Sema3A Modified PDLSCs Exhibited Enhanced Osteogenic Capabilities and Stimulated Differentiation of Pre-Osteoblasts. Cell Biochem Biophys 2023; 81:543-552. [PMID: 37421591 DOI: 10.1007/s12013-023-01148-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 06/23/2023] [Indexed: 07/10/2023]
Abstract
Genetically engineered stem cells, not only acting as vector delivering growth factors or cytokines but also exhibiting improved cell properties, are promising cells for periodontal tissue regeneration. Sema3A is a power secretory osteoprotective factor. In this study, we aimed to construct Sema3A modified periodontal ligament stem cells (PDLSCs) and evaluated their osteogenic capability and crosstalk with pre-osteoblasts MC3T3-E1. First, Sema3A modified PDLSCs was constructed using lentivirus infection system carrying Sema3A gene and the transduction efficiency was analyzed. The osteogenic differentiation and proliferation of Sema3A-PDLSCs was evaluated. Then, MC3T3-E1 was directly co-cultured with Sema3A-PDLSCs or cultured in condition medium of Sema3A-PDLSCs and the osteogenic ability of MC3T3-E1 was assessed. The results showed that Sema3A-PDLSCs expressed and secreted upregulated Sema3A protein, which confirmed successful construction of Sema3A modified PDLSCs. After osteogenic induction, Sema3A-PDLSCs expressed upregulated ALP, OCN, RUNX2, and SP7 mRNA, expressed higher ALP activity, and produced more mineralization nodes, compared with Vector-PDLSCs. Whereas, there was no obvious differences in proliferation between Sema3A-PDLSCs and Vector-PDLSCs. MC3T3-E1 expressed upregulated mRNA of ALP, OCN, RUNX2, and SP7 when directly co-cultured with Sema3A-PDLSCs than Vector-PDLSCs. MC3T3-E1 also expressed upregulated osteogenic markers, showed higher ALP activity, and produced more mineralization nodes when cultured using condition medium of Sema3A-PDLSCs instead of Vector-PDLSCs. In conclusion, our results indicated that Sema3A modified PDLSCs showed enhanced osteogenic capability, and also facilitated differentiation of pre-osteoblasts.
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Affiliation(s)
- Wen Wang
- School of Stomatology, Xuzhou Medical University, Xuzhou, China
- Affiliated Stomatological Hospital of Xuzhou Medical University, Xuzhou, China
| | - Banghui Chen
- School of Stomatology, Xuzhou Medical University, Xuzhou, China
- Affiliated Stomatological Hospital of Xuzhou Medical University, Xuzhou, China
| | - Jintao Yang
- School of Stomatology, Xuzhou Medical University, Xuzhou, China
| | - Yizhou Li
- School of Stomatology, Xuzhou Medical University, Xuzhou, China
| | - Haonan Ding
- School of Stomatology, Nanjing Medical University, Nanjing, China
| | - Hao Liu
- School of Stomatology, Xuzhou Medical University, Xuzhou, China.
- Affiliated Stomatological Hospital of Xuzhou Medical University, Xuzhou, China.
| | - Changyong Yuan
- School of Stomatology, Xuzhou Medical University, Xuzhou, China.
- Affiliated Stomatological Hospital of Xuzhou Medical University, Xuzhou, China.
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18
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Hjazi A, Sukmana BI, Ali SS, Alsaab HO, Gupta J, Ullah MI, Romero-Parra RM, Alawadi AHR, Alazbjee AAA, Mustafa YF. Functional role of circRNAs in osteogenesis: A review. Int Immunopharmacol 2023; 121:110455. [PMID: 37290324 DOI: 10.1016/j.intimp.2023.110455] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/23/2023] [Revised: 05/20/2023] [Accepted: 06/02/2023] [Indexed: 06/10/2023]
Abstract
The extracellular matrixes (ECM), as well as the microenvironmental signals, play an essential role in osteogenesis by regulating intercellular pathways. Recently, it has been demonstrated that a newly identified RNA, circular RNA, contributes to the osteogenesis process. Circular RNA (circRNA), the most recently identified RNA, is involved in the regulation of gene expression at transcription to translation levels. The dysregulation of circRNAs has been observed in several tumors and diseases. Also, various studies have shown that circRNAs expression is changed during osteogenic differentiation of progenitor cells. Therefore, understanding the role of circRNAs in osteogenesis might help the diagnosis as well as treatment of bone diseases such as bone defects and osteoporosis. In this review, circRNA functions and the related pathways in osteogenesis have been discussed.
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Affiliation(s)
- Ahmed Hjazi
- Department of Medical Laboratory Sciences, College of Applied Medical Sciences, Prince Sattam bin Abdulaziz University, Al-Kharj 11942, Saudi Arabia
| | - Bayu Indra Sukmana
- Department of Oral Biology, Faculty of Dentistry, Lambung Mangkurat University, Banjarmasin, Indonesia
| | - Sally Saad Ali
- College of Dentistry, Al-Bayan University, Baghdad, Iraq
| | - Hashem O Alsaab
- Pharmaceutics and Pharmaceutical Technology, Taif University, Taif, Saudi Arabia
| | - Jitendra Gupta
- Institute of Pharmaceutical Research, GLA University, Mathura, Pin Code 281406 U.P., India
| | - Muhammad Ikram Ullah
- Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, Jouf University, Sakaka 75471, Aljouf, Saudi Arabia
| | | | - Ahmed H R Alawadi
- Medical Analysis Department, College of Medical Technology, The Islamic University, Najaf, Iraq
| | | | - Yasser Fakri Mustafa
- Department of Pharmaceutical Chemistry, College of Pharmacy, University of Mosul, Mosul-41001, Iraq
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19
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Wu J, Zhang L, Liu H, Zhang J, Tang P. Exosomes promote hFOB1.19 proliferation and differentiation via LINC00520. J Orthop Surg Res 2023; 18:546. [PMID: 37516879 PMCID: PMC10387216 DOI: 10.1186/s13018-023-04021-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/13/2023] [Accepted: 07/15/2023] [Indexed: 07/31/2023] Open
Abstract
BACKGROUND Osteoporosis remains a significant clinical challenge worldwide. Recent studies have shown that exosomes stimulate bone regeneration. Thus, it is worthwhile to explore whether exosomes could be a useful therapeutic strategy for osteoporosis. The purpose of this study was to investigate the effects of exosomes derived from human umbilical cord mesenchymal stem cells (hucMSCs) on osteoblast proliferation and differentiation. METHODS Exosomes were isolated from hucMSCs. Bioinformatics analysis was performed to identify the differentially expressed lncRNAs in myeloma-derived mesenchymal stem cells. Plasmids encoding LINC00520 or short hairpin RNA of LINC00520 were transfected into hucMSCs and then exosomes were isolated. After human osteoblasts hFOB1.19 were exposed to the obtained exosomes, cell survival, cell cycle, apoptosis and calcium deposits of hFOB1.19 cell were detected by MTT, 7-aminoactinomycin D, Annexin V-FITC/propidium iodide and Alizarin red staining, respectively. RESULTS In hFOB1.19 cells, 10 × 109/mL hucMSC-derived exosomes inhibited cell proliferation, arrested cell cycle, and promoted apoptosis, while hucMSCs or 1 × 109/mL exosomes promoted cell proliferation, accelerated cell cycle, and promoted calcium deposits and the expression of OCN, RUNX2, collagen I and ALP. In hFOB1.19 cells, exosomes from hucMSCs with LINC00520 knockdown reduced the survival and calcium deposits, arrested the cell cycle, and enhanced the apoptosis, while exosomes from hucMSCs overexpressing LINC00520 enhance the proliferation and calcium deposits and accelerated the cell cycle. CONCLUSIONS LINC00520 functions as a modulator of calcium deposits, and exosomes derived from hucMSCs overexpressing LINC00520 might be a novel therapeutic approach for osteoporosis.
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Affiliation(s)
- Jin Wu
- Medical School of Chinese PLA, Chinese PLA General Hospital, No. 28 Fuxing Road, Haidian District, Beijing, 100853, China
- Department of Orthopedics, National Clinical Research Center for Orthopedics, Sports Medicine and Rehabilitation, Chinese PLA General Hospital, Beijing, 100853, China
- Department of Orthopedics, The 909th Hospital, School of Medicine, Xiamen University, Zhangzhou, 363000, China
| | - Licheng Zhang
- Medical School of Chinese PLA, Chinese PLA General Hospital, No. 28 Fuxing Road, Haidian District, Beijing, 100853, China.
- Department of Orthopedics, National Clinical Research Center for Orthopedics, Sports Medicine and Rehabilitation, Chinese PLA General Hospital, Beijing, 100853, China.
| | - Hui Liu
- Department of Orthopedics, The 909th Hospital, School of Medicine, Xiamen University, Zhangzhou, 363000, China
| | - Jinhui Zhang
- Department of Orthopedics, The 909th Hospital, School of Medicine, Xiamen University, Zhangzhou, 363000, China
| | - Peifu Tang
- Medical School of Chinese PLA, Chinese PLA General Hospital, No. 28 Fuxing Road, Haidian District, Beijing, 100853, China.
- Department of Orthopedics, National Clinical Research Center for Orthopedics, Sports Medicine and Rehabilitation, Chinese PLA General Hospital, Beijing, 100853, China.
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20
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Zhang Z, Cui S, Fu Y, Wang J, Liu J, Wei F. Mechanical force induces mitophagy-mediated anaerobic oxidation in periodontal ligament stem cells. Cell Mol Biol Lett 2023; 28:57. [PMID: 37480044 PMCID: PMC10362665 DOI: 10.1186/s11658-023-00453-w] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/06/2023] [Accepted: 04/18/2023] [Indexed: 07/23/2023] Open
Abstract
BACKGROUND The preference for glucose oxidative mode has crucial impacts on various physiological activities, including determining stem cell fate. External mechanical factors can play a decisive role in regulating critical metabolic enzymes and pathways of stem cells. Periodontal ligament stem cells (PDLSCs) are momentous effector cells that transform mechanical force into biological signals during the reconstruction of alveolar bone. However, mechanical stimuli-induced alteration of oxidative characteristics in PDLSCs and the underlying mechanisms have not been fully elucidated. METHODS Herein, we examined the expression of LDH and COX4 by qRT-PCR, western blot, immunohistochemistry and immunofluorescence. We detected metabolites of lactic acid and reactive oxygen species for functional tests. We used tetramethylrhodamine methyl ester (TMRM) staining and a transmission electron microscope to clarify the mitochondrial status. After using western blot and immunofluorescence to clarify the change of DRP1, we further examined MFF, PINK1, and PARKIN by western blot. We used cyclosporin A (CsA) to confirm the regulation of mitophagy and ceased the stretching as a rescue experiment. RESULTS Herein, we ascertained that mechanical force could increase the level of LDH and decrease the expression of COX4 in PDLSCs. Simultaneously, the yield of reactive oxygen species (ROS) in PDLSC reduced after stretching, while lactate acid augmented significantly. Furthermore, mitochondrial function in PDLSCs was negatively affected by impaired mitochondrial membrane potential (MMP) under mechanical force, and the augment of mitochondrial fission further induced PRKN-dependent mitophagy, which was confirmed by the rescue experiments via blocking mitophagy. As a reversible physiological stimulation, the anaerobic preference of PDLSCs altered by mechanical force could restore after the cessation of force stimulation. CONCLUSIONS Altogether, our study demonstrates that PDLSCs under mechanical force preferred anaerobic oxidation induced by the affected mitochondrial dynamics, especially mitophagy. Our findings support an association between mechanical stimulation and the oxidative profile of stem cells, which may shed light on the mechanical guidance of stem cell maintenance and commitment, and lay a molecular foundation for periodontal tissue regeneration.
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Affiliation(s)
- Zijie Zhang
- Department of Orthodontics, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University & Shandong Key Laboratory of Oral Tissue Regeneration & Shandong Engineering Laboratory for Dental Materials and Oral Tissue Regeneration & Shandong Provincial Clinical Research Center for Oral Diseases, Shandong University Cheeloo College of Medicine, No.44-1 Wenhua Road West, Jinan, 250012, Shandong, China
| | - Shuyue Cui
- Department of Orthodontics, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University & Shandong Key Laboratory of Oral Tissue Regeneration & Shandong Engineering Laboratory for Dental Materials and Oral Tissue Regeneration & Shandong Provincial Clinical Research Center for Oral Diseases, Shandong University Cheeloo College of Medicine, No.44-1 Wenhua Road West, Jinan, 250012, Shandong, China
| | - Yajing Fu
- Department of Orthodontics, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University & Shandong Key Laboratory of Oral Tissue Regeneration & Shandong Engineering Laboratory for Dental Materials and Oral Tissue Regeneration & Shandong Provincial Clinical Research Center for Oral Diseases, Shandong University Cheeloo College of Medicine, No.44-1 Wenhua Road West, Jinan, 250012, Shandong, China
| | - Jixiao Wang
- Department of Orthodontics, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University & Shandong Key Laboratory of Oral Tissue Regeneration & Shandong Engineering Laboratory for Dental Materials and Oral Tissue Regeneration & Shandong Provincial Clinical Research Center for Oral Diseases, Shandong University Cheeloo College of Medicine, No.44-1 Wenhua Road West, Jinan, 250012, Shandong, China
| | - Jiani Liu
- Department of Orthodontics, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University & Shandong Key Laboratory of Oral Tissue Regeneration & Shandong Engineering Laboratory for Dental Materials and Oral Tissue Regeneration & Shandong Provincial Clinical Research Center for Oral Diseases, Shandong University Cheeloo College of Medicine, No.44-1 Wenhua Road West, Jinan, 250012, Shandong, China
| | - Fulan Wei
- Department of Orthodontics, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University & Shandong Key Laboratory of Oral Tissue Regeneration & Shandong Engineering Laboratory for Dental Materials and Oral Tissue Regeneration & Shandong Provincial Clinical Research Center for Oral Diseases, Shandong University Cheeloo College of Medicine, No.44-1 Wenhua Road West, Jinan, 250012, Shandong, China.
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21
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Moura SR, Fernandes MJ, Santos SG, Almeida MI. Circular RNAs: Promising Targets in Osteoporosis. Curr Osteoporos Rep 2023; 21:289-302. [PMID: 37119447 PMCID: PMC10169890 DOI: 10.1007/s11914-023-00786-7] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 03/21/2023] [Indexed: 05/01/2023]
Abstract
PURPOSE OF REVIEW Circular RNAs (circRNAs) are RNA transcripts derived from fragments of pre-messenger RNAs through a back-splicing process. An advantage that rises from their circular covalently closed conformation is their high stability, when compared with their linear counterparts. The current review focuses on the emerging roles of circRNAs in osteoporosis, including in osteogenic differentiation and osteoclastogenesis. Their potential as osteoporosis biomarkers will also be discussed. RECENT FINDINGS Although firstly described as non-coding, some of these single-stranded RNAs were recently reported to possess protein-coding capacity. On the other hand, the circRNAs exhibit cell and tissue-specific patterns at the transcriptome level in eukaryotes and are regulated throughout the development or disease progression. Even though thousands of these circular transcripts are listed and annotated, only a limited number of studies describe their biological role in bone processes. Recent evidence indicates inhibitory activator roles in both osteoblasts and osteoclasts differentiation and function. Latest screenings in the blood, plasma, or serum of osteoporosis patients support the potential for circRNA signature to be used as biomarkers in osteoporosis, but further validation is required. While intense research into circRNAs has been detailing their biological roles, there remains a need for standardization and further research to fulfil the future potential of this emerging and highly promising class of regulatory molecules.
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Affiliation(s)
- Sara Reis Moura
- i3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, Portugal
- INEB - Instituto de Engenharia Biomédica, Universidade do Porto, Porto, Portugal
- ICBAS - Instituto de Ciências Biomédicas Abel Salazar, Universidade do Porto, Porto, Portugal
| | - Maria João Fernandes
- i3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, Portugal
- INEB - Instituto de Engenharia Biomédica, Universidade do Porto, Porto, Portugal
- ICBAS - Instituto de Ciências Biomédicas Abel Salazar, Universidade do Porto, Porto, Portugal
| | - Susana G Santos
- i3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, Portugal.
- INEB - Instituto de Engenharia Biomédica, Universidade do Porto, Porto, Portugal.
| | - Maria Inês Almeida
- i3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, Portugal
- INEB - Instituto de Engenharia Biomédica, Universidade do Porto, Porto, Portugal
- ICBAS - Instituto de Ciências Biomédicas Abel Salazar, Universidade do Porto, Porto, Portugal
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22
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Al-Hawary SIS, Asghar W, Amin A, Mustafa YF, Hjazi A, Almulla AF, Ali SAJ, Ali SS, Romero-Parra RM, Abdulhussien Alazbjee AA, Mahmoudi R, Fard SRH. Circ_0067934 as a novel therapeutic target in cancer: From mechanistic to clinical perspectives. Pathol Res Pract 2023; 245:154469. [PMID: 37100022 DOI: 10.1016/j.prp.2023.154469] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/15/2023] [Revised: 04/12/2023] [Accepted: 04/18/2023] [Indexed: 04/28/2023]
Abstract
Circular RNAs, as a type of non-coding RNAs, are identified in a various cell. Circular RNAs have stable structures, conserved sequence, and tissue and cell-specific level. High throughput technologies have proposed that circular RNAs act via various mechanisms like sponging microRNAs and proteins, regulating transcription factors, and scaffolding mediators. Cancer is one of the major threat for human health. Emerging data have proposed that circular RNAs are dysregulated in cancers as well as are associated with aggressive behaviors of cancer -related behaviors like cell cycle, proliferation, apoptosis, invasion, migration, and epithelial-mesenchymal transition (EMT). Among them, circ_0067934 was shown to act as an oncogene in cancers to enhance migration, invasion, proliferation, cell cycle, EMT, and inhibit cell apoptosis. In addition, these studies have proposed that it could be a promising diagnostic and prognostic biomarker in cancer. This study aimed to review the expression and molecular mechanism of circ_0067934 in modulating the malignant behaviors of cancers as well as to explore its potential as a target in cancer chemotherapy, diagnosis, prognosis and treatment.
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Affiliation(s)
| | | | - Aaima Amin
- Quaid e Azam Medical College, Bahawal Victorial Hospital, Bahawalpur, Pakistan
| | - Yasser Fakri Mustafa
- Department of Pharmaceutical Chemistry, College of Pharmacy, University of Mosul, Mosul 41001, Iraq
| | - Ahmed Hjazi
- Department of Medical Laboratory Sciences, College of Applied Medical Sciences, Prince Sattam bin Abdulaziz University, Al-Kharj 11942, Saudi Arabia
| | - Abbas F Almulla
- Medical Laboratory Technology Department, College of Medical Technology, The Islamic University, Najaf, Iraq
| | | | - Sally Saad Ali
- College of Dentistry, Al-Bayan University, Baghdad, Iraq
| | | | | | - Reza Mahmoudi
- Department of Toxicology and Pharmacology, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.
| | - Seyed Reza Hosseini Fard
- Department of Biochemistry, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
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23
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Zhang C, Xue P, Ke J, Cai Q. Development of Ferroptosis-Associated ceRNA Network in Periodontitis. Int Dent J 2023; 73:186-194. [PMID: 35810010 PMCID: PMC10023542 DOI: 10.1016/j.identj.2022.05.004] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/09/2022] [Revised: 05/05/2022] [Accepted: 05/07/2022] [Indexed: 12/13/2022] Open
Abstract
OBJECTIVES Periodontitis is a chronic inflammatory illness that may lead to tooth loosening and even loss, and its pathogenesis is not fully understood. Ferroptosis is an iron-dependent, regulated cell death. The present study aims to find the key ferroptosis-related genes (FRGs) in periodontitis and develop an mRNA-miRNA-lncRNA network to deeply explore the pathogenesis of periodontitis. METHODS Data from the Gene Expression Omnibus (GEO) database and FerrDb database were downloaded to discover the differentially expressed mRNA, miRNA, and FRGs. Functional enrichment analysis was conducted for the differentially expressed FRGs (DE-FRGs), including gene ontology, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway, and protein-protein interaction (PPI) network analysis. Targetscan and miRtarbase were used to estimate the miRNAs that DE-FRGs may interact with, whilst StarBase v3.0 was used for lncRNA-miRNA interaction. RESULTS Seven DE-FRGs were identified through differential expression analysis. Interleukin 1 beta (IL1B) interacted with XBP1 and MMP13 in the PPI network. After taking the intersection between DE-miRNAs and predicted miRNAs, a ceRNA network containing IL1B, has-miR-185, has-miR-204, has-miR-211, has-miR-4306, and 28 lncRNAs was established. CONCLUSIONS Seven FRGs in periodontitis were identified, which might promote deeper understanding of ferroptosis in periodontitis.
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Affiliation(s)
- Churen Zhang
- Department of Stomatology, The First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, China.
| | - Pengxin Xue
- The Ninth People's Hospital Affiliated to Shanghai Jiao Tong University.
| | - Jianguo Ke
- Department of Stomatology, The First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, China.
| | - Qiaoling Cai
- Department of Stomatology, The First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, China.
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Ye Y, Fu L, Liu L, Xiao T, Cuba Manduca AG, Yu J. Integrative Analysis of ceRNA Networks in human periodontal ligament stem cells under hypoxia. Oral Dis 2023; 29:1197-1213. [PMID: 34874587 DOI: 10.1111/odi.14096] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/05/2021] [Revised: 11/11/2021] [Accepted: 12/01/2021] [Indexed: 11/30/2022]
Abstract
OBJECTIVE This study aims to investigate the regulatory effect of hypoxia on human periodontal ligament stem cells (PDLSCs) through RNA sequencing (RNA SEQ). Human PDLSCs were cultured in normoxia (20% O2 ) or hypoxia (2% O2 ). MATERIAL AND METHODS Total RNA was extracted and sequenced. The expression profiles of circRNAs, lncRNAs, and miRNAs were determined, and the lncRNA/circRNA-miRNA-mRNA networks were analyzed. RESULTS In total, 15 miRNAs, 449 lncRNAs, and 53 circRNAs were differentially expressed. Among them, 21 circRNAs, 262 lncRNAs, 5 miRNAs, and 5 mRNAs were selected to construct competing endogenous RNA (ceRNA) networks. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were carried out to explore potential related pathways and regulatory functions. Several ceRNA axes (lncRNA-FTX/circRNA-FAT1-hsa-miR-4781-3p-SMAD5 and circRNA LPAR1-hsa-miR-342-3p-ADAR) may provide a theoretical basis on the study of osteogenic differentiation of PDLSCs under hypoxia. CONCLUSION This study revealed that the expression profiles of circRNAs, lncRNAs, and miRNAs had changed significantly in PDLSCs cultured in 2% O2 ; specific circRNAs/lncRNAs may play a competitive role in the differentiation of PDLSCs.
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Affiliation(s)
- Yu Ye
- Jiangsu Key Laboratory of Oral Diseases, Nanjing Medical University & Department of Endodontic, Affiliated Hospital of Stomatology, Nanjing Medical University, Nanjing, China
- Institute of Stomatology, Nanjing Medical University, Nanjing, China
| | - Lin Fu
- Jiangsu Key Laboratory of Oral Diseases, Nanjing Medical University & Department of Endodontic, Affiliated Hospital of Stomatology, Nanjing Medical University, Nanjing, China
- Institute of Stomatology, Nanjing Medical University, Nanjing, China
| | - Liu Liu
- Jiangsu Key Laboratory of Oral Diseases, Nanjing Medical University & Department of Endodontic, Affiliated Hospital of Stomatology, Nanjing Medical University, Nanjing, China
- Institute of Stomatology, Nanjing Medical University, Nanjing, China
| | - Tong Xiao
- Jiangsu Key Laboratory of Oral Diseases, Nanjing Medical University & Department of Endodontic, Affiliated Hospital of Stomatology, Nanjing Medical University, Nanjing, China
- Institute of Stomatology, Nanjing Medical University, Nanjing, China
| | - Ana Gloria Cuba Manduca
- Jiangsu Key Laboratory of Oral Diseases, Nanjing Medical University & Department of Endodontic, Affiliated Hospital of Stomatology, Nanjing Medical University, Nanjing, China
- Institute of Stomatology, Nanjing Medical University, Nanjing, China
| | - Jinhua Yu
- Jiangsu Key Laboratory of Oral Diseases, Nanjing Medical University & Department of Endodontic, Affiliated Hospital of Stomatology, Nanjing Medical University, Nanjing, China
- Institute of Stomatology, Nanjing Medical University, Nanjing, China
- Jiangsu Province Engineering Research Center of Stomatological Translational Medicine, Nanjing, China
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25
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Pan Y, Liu Y, Wei W, Yang X, Wang Z, Xin W. Extracellular Vesicles as Delivery Shippers for Noncoding RNA-Based Modulation of Angiogenesis: Insights from Ischemic Stroke and Cancer. SMALL (WEINHEIM AN DER BERGSTRASSE, GERMANY) 2023; 19:e2205739. [PMID: 36592424 DOI: 10.1002/smll.202205739] [Citation(s) in RCA: 14] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/17/2022] [Revised: 12/02/2022] [Indexed: 06/17/2023]
Abstract
Ischemic stroke and systemic cancer are two of the leading causes of mortality. Hypoxia is a central pathophysiological component in ischemic stroke and cancer, representing a joint medical function. This function includes angiogenesis regulation. Vascular remodeling coupled with axonal outgrowth following cerebral ischemia is critical in improving poststroke neurological functional recovery. Antiangiogenic strategies can inhibit cancer vascularization and play a vital role in impeding cancer growth, invasion, and metastasis. Although there are significant differences in the cause of angiogenesis across both pathophysiological conditions, emerging evidence states that common signaling structures, such as extracellular vesicles (EVs) and noncoding RNAs (ncRNAs), are involved in this context. EVs, heterogeneous membrane vesicles encapsulating proteomic genetic information from parental cells, act as multifunctional regulators of intercellular communication. Among the multifaceted roles in modulating biological responses, exhaustive evidence shows that ncRNAs are selectively sorted into EVs, modulating common specific aspects of cancer development and stroke prognosis, namely, angiogenesis. This review will discuss recent advancements in the EV-facilitated/inhibited progression of specific elements of angiogenesis with a particular concern about ncRNAs within these vesicles. The review is concluded by underlining the clinical opportunities of EV-derived ncRNAs as diagnostic, prognostic, and therapeutic agents.
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Affiliation(s)
- Yongli Pan
- Department of Neurology, University Medical Center of Göttingen, Georg-August-University of Göttingen, 37075, Göttingen, Lower Saxony, Germany
- Department of Neurology, Weifang Medical University, Weifang, Shandong, 261053, China
| | - Yuheng Liu
- Department of Neurosurgery, Tianjin Medical University General Hospital, Tianjin, 300052, China
- Tianjin Neurological Institute, Tianjin, 300052, China
| | - Wei Wei
- Department of Neurology, University Medical Center of Göttingen, Georg-August-University of Göttingen, 37075, Göttingen, Lower Saxony, Germany
- Department of Neurology, Mianyang Central Hospital, Mianyang, Sichuan, 621000, China
| | - Xinyu Yang
- Department of Neurosurgery, Tianjin Medical University General Hospital, Tianjin, 300052, China
- Tianjin Neurological Institute, Tianjin, 300052, China
| | - Zengguang Wang
- Department of Neurosurgery, Tianjin Medical University General Hospital, Tianjin, 300052, China
- Tianjin Neurological Institute, Tianjin, 300052, China
| | - Wenqiang Xin
- Department of Neurology, University Medical Center of Göttingen, Georg-August-University of Göttingen, 37075, Göttingen, Lower Saxony, Germany
- Department of Neurosurgery, Tianjin Medical University General Hospital, Tianjin, 300052, China
- Tianjin Neurological Institute, Tianjin, 300052, China
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Jia L, Li D, Wang YN, Zhang D, Xu X. PSAT1 positively regulates the osteogenic lineage differentiation of periodontal ligament stem cells through the ATF4/PSAT1/Akt/GSK3β/β-catenin axis. J Transl Med 2023; 21:70. [PMID: 36732787 PMCID: PMC9893676 DOI: 10.1186/s12967-022-03775-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/14/2022] [Accepted: 11/15/2022] [Indexed: 02/04/2023] Open
Abstract
BACKGROUND Periodontal ligament stem cells (PDLSCs) are important seed cells for tissue engineering to realize the regeneration of alveolar bone. Understanding the gene regulatory mechanisms of osteogenic lineage differentiation in PDLSCs will facilitate PDLSC-based bone regeneration. However, these regulatory molecular signals have not been clarified. METHODS To screen potential regulators of osteogenic differentiation, the gene expression profiles of undifferentiated and osteodifferentiated PDLSCs were compared by microarray and bioinformatics methods, and PSAT1 was speculated to be involved in the gene regulation network of osteogenesis in PDLSCs. Lentiviral vectors were used to overexpress or knock down PSAT1 in PDLSCs, and then the proliferation activity, migration ability, and osteogenic differentiation ability of PDLSCs in vitro were analysed. A rat mandibular defect model was built to analyse the regulatory effects of PSAT1 on PDLSC-mediated bone regeneration in vivo. The regulation of PSAT1 on the Akt/GSK3β/β-catenin signalling axis was analysed using the Akt phosphorylation inhibitor Ly294002 or agonist SC79. The potential sites on the promoter of PSAT1 that could bind to the transcription factor ATF4 were predicted and verified. RESULTS The microarray assay showed that the expression levels of 499 genes in PDLSCs were altered significantly after osteogenic induction. Among these genes, the transcription level of PSAT1 in osteodifferentiated PDLSCs was much lower than that in undifferentiated PDLSCs. Overexpressing PSAT1 not only enhanced the proliferation and osteogenic differentiation abilities of PDLSCs in vitro, but also promoted PDLSC-based alveolar bone regeneration in vivo, while knocking down PSAT1 had the opposite effects in PDLSCs. Mechanistic experiments suggested that PSAT1 regulated the osteogenic lineage fate of PDLSCs through the Akt/GSK3β/β-catenin signalling axis. PSAT1 expression in PDLSCs during osteogenic differentiation was controlled by transcription factor ATF4, which is realized by the combination of ATF4 and the PSAT1 promoter. CONCLUSION PSAT1 is a potential important regulator of the osteogenic lineage differentiation of PDLSCs through the ATF4/PSAT1/Akt/GSK3β/β-catenin signalling pathway. PSAT1 could be a candidate gene modification target for enhancing PDLSCs-based bone regeneration.
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Affiliation(s)
- Linglu Jia
- grid.27255.370000 0004 1761 1174Department of Prosthodontics, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University, Jinan, China ,Shandong Key Laboratory of Oral Tissue Regeneration, Jinan, China ,Shandong Engineering Laboratory for Dental Materials and Oral Tissue Regeneration, Jinan, China ,Shandong Provincial Clinical Research Center for Oral Diseases, Jinan, China
| | - Dongfang Li
- Shandong Key Laboratory of Oral Tissue Regeneration, Jinan, China ,Shandong Engineering Laboratory for Dental Materials and Oral Tissue Regeneration, Jinan, China ,Shandong Provincial Clinical Research Center for Oral Diseases, Jinan, China
| | - Ya-Nan Wang
- grid.27255.370000 0004 1761 1174Department of Implantology, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University, No. 44-1 Wenhua Road West, Jinan, 250012 Shandong China ,Shandong Key Laboratory of Oral Tissue Regeneration, Jinan, China ,Shandong Engineering Laboratory for Dental Materials and Oral Tissue Regeneration, Jinan, China ,Shandong Provincial Clinical Research Center for Oral Diseases, Jinan, China
| | - Dongjiao Zhang
- Department of Implantology, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University, No. 44-1 Wenhua Road West, Jinan, 250012, Shandong, China. .,Shandong Key Laboratory of Oral Tissue Regeneration, Jinan, China. .,Shandong Engineering Laboratory for Dental Materials and Oral Tissue Regeneration, Jinan, China. .,Shandong Provincial Clinical Research Center for Oral Diseases, Jinan, China.
| | - Xin Xu
- Department of Implantology, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University, No. 44-1 Wenhua Road West, Jinan, 250012, Shandong, China. .,Shandong Key Laboratory of Oral Tissue Regeneration, Jinan, China. .,Shandong Engineering Laboratory for Dental Materials and Oral Tissue Regeneration, Jinan, China. .,Shandong Provincial Clinical Research Center for Oral Diseases, Jinan, China.
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27
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Zhu Y, Yan W, Xu S, Yu X, Sun S, Zhang S, Zhao R, Tao J, Li Y, Li C. Identification of an unrecognized circRNA associated with development of renal fibrosis. Front Genet 2023; 13:964840. [PMID: 36685959 PMCID: PMC9845265 DOI: 10.3389/fgene.2022.964840] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/09/2022] [Accepted: 12/01/2022] [Indexed: 01/05/2023] Open
Abstract
Backgroud: Renal fibrosis is the common characteristic of chronic kidney disease. Circular RNA plays an essential role in the occurrence and development of Renal fibrosis, but its regulative mechanism remains elusive. Methods: The animal and cell model of Renal fibrosis was established, and RNA-sequencing and real-time polymerase chain reaction (qRT-PCR) experiments were implemented. Subsequently, experiments for detecting apoptosis and proliferation of cell, were carried out, and the isobaric tags for relative and absolute quantification proteomics analyses were performed accordingly. Results: It was found that a newly discovered Circular RNA (circRNA_0002158), is highly expressed in kidneys or cells with fibrosis, implying that this Circular RNA might be associated with the occurrence and development of Renal fibrosis. Subsequently, the overexpression and knockdown of circRNA_0002158 were conducted in the human kidney epithelial cell line (HK-2) cells, and the results indicated that the circRNA_0002158 could inhibit apoptosis, and promote proliferation of cells. The kidney injury-related factors, including Fibronectin and plasminogen activator inhibitor-1 (PAI-1), were decreased in HK-2 cells with overexpression of circRNA_0002158, while the results were reversed in cells with knockdown of circRNA_0002158. Finally, to explore the regulative mechanism of circRNA_0002158, the iTRAQ proteomics analyses were implemented for the cell samples with OE of circRNA_0002158 and its control, it showed that multiple genes and functional pathways were associated with the occurrence and development of Renal fibrosis. Conclusion: CircRNA_0002158 is associated with regulating Renal fibrosis, and may contribute to ameliorating the progression of Renal fibrosis in the future.
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Affiliation(s)
- Yun Zhu
- Department of Dermatology, The People’s Hospital of Yuxi City, Yuxi, China
| | - Weimin Yan
- Department of Dermatology, The People’s Hospital of Yuxi City, Yuxi, China
| | - Shuangyan Xu
- Department of Dermatology, The People’s Hospital of Yuxi City, Yuxi, China
| | - Xiaochao Yu
- Graduate School, Kunming Medical University, Kunming, China
| | - Shuo Sun
- Graduate School, Kunming Medical University, Kunming, China
| | | | - Ran Zhao
- Graduate School, Kunming Medical University, Kunming, China
| | - Jiayue Tao
- Graduate School, Kunming Medical University, Kunming, China
| | - Yunwei Li
- Department of Urology, The Third Hospital of Shandong Province, Jinan, China,*Correspondence: Yunwei Li, ; Cuie Li,
| | - Cuie Li
- Department of Geriatrics, The People’s Hospital of Yuxi City, Yuxi, China,*Correspondence: Yunwei Li, ; Cuie Li,
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Chen Y, Wang X, Wu Z, Jia S, Wan M. Epigenetic regulation of dental-derived stem cells and their application in pulp and periodontal regeneration. PeerJ 2023; 11:e14550. [PMID: 36620748 PMCID: PMC9817962 DOI: 10.7717/peerj.14550] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/29/2022] [Accepted: 11/20/2022] [Indexed: 01/05/2023] Open
Abstract
Dental-derived stem cells have excellent proliferation ability and multi-directional differentiation potential, making them an important research target in tissue engineering. An increasing number of dental-derived stem cells have been discovered recently, including dental pulp stem cells (DPSCs), stem cells from exfoliated deciduous teeth (SHEDs), stem cells from apical papilla (SCAPs), dental follicle precursor cells (DFPCs), and periodontal ligament stem cells (PDLSCs). These stem cells have significant application prospects in tissue regeneration because they are found in an abundance of sources, and they have good biocompatibility and are highly effective. The biological functions of dental-derived stem cells are regulated in many ways. Epigenetic regulation means changing the expression level and function of a gene without changing its sequence. Epigenetic regulation is involved in many biological processes, such as embryonic development, bone homeostasis, and the fate of stem cells. Existing studies have shown that dental-derived stem cells are also regulated by epigenetic modifications. Pulp and periodontal regeneration refers to the practice of replacing damaged pulp and periodontal tissue and restoring the tissue structure and function under normal physiological conditions. This treatment has better therapeutic effects than traditional treatments. This article reviews the recent research on the mechanism of epigenetic regulation of dental-derived stem cells, and the core issues surrounding the practical application and future use of pulp and periodontal regeneration.
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Affiliation(s)
- Yuyang Chen
- State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases & West China School of Stomatology, Sichuan University, Chengdu, Sichuan, People’s Republic of China
| | - Xiayi Wang
- State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases & West China School of Stomatology, Sichuan University, Chengdu, Sichuan, People’s Republic of China
| | - Zhuoxuan Wu
- State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases & West China School of Stomatology, Sichuan University, Chengdu, Sichuan, People’s Republic of China
| | - Shiyu Jia
- State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases & West China School of Stomatology, Sichuan University, Chengdu, Sichuan, People’s Republic of China
| | - Mian Wan
- State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases & West China School of Stomatology, Sichuan University, Chengdu, Sichuan, People’s Republic of China,State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases & Department of Cariology and Endodontics, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan, People’s Republic of China
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lncRNA CYTOR Facilitates Osteogenic Differentiation of Human Periodontal Ligament Stem Cells by Modulating SOX11 via Sponging miR-6512-3p. Stem Cells Int 2023; 2023:5671809. [PMID: 36910334 PMCID: PMC10005871 DOI: 10.1155/2023/5671809] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2022] [Revised: 01/26/2023] [Accepted: 02/15/2023] [Indexed: 03/06/2023] Open
Abstract
Periodontal ligament stem cells (PDLSCs) are considered ideal cell sources for the regeneration of periodontal and alveolar bone tissue. Cytoskeleton Regulator RNA (CYTOR), a newly discovered long noncoding RNA, has been reported to function as competing endogenous RNA (ceRNA) and to be involved in many biological processes. However, its roles in PDLSC osteogenic differentiation remain unclear. Here, we firstly found CYTOR was mainly sublocalized in the cytoplasm of PDLSCs and CYTOR expression was increased during osteogenic differentiation of PDLSCs. By employing gain- and loss-of-function approaches, we then identified CYTOR overexpression promoted osteogenic differentiation of PDLSCs while CYTOR knockdown inhibited this process. Furthermore, bioinformatics analysis was utilized to show that both CYTOR and SOX11 mRNA contained the same seed sites for miR-6512-3p, which was further confirmed by dual luciferase reporter assay and RNA-binding protein immunoprecipitation. Notably, CYTOR conferred its functions by directly binding to miR-6512-3p and an inverse correlation between CYTOR and miR-6512-3p on the level on SOX11 and osteogenic differentiation of PDLSCs was obtained. Additionally, miR-6512-3p could bind to SOX11 mRNA 3' UTR and repressed SOX11 expression. Moreover, level of SOX11 was significantly increased during osteogenic differentiation of PDLSCs. Knockdown of SOX11 attenuated the increasing effect of CYTOR overexpression on osteogenic differentiation of PDLSCs. Collectively, these data supported that CYTOR positively modulated the expression of SOX11 through competitively binding to miR-6512-3p, thus promoting osteogenic differentiation of PDLSCs. The CYTOR/miR-6512-3p/SOX11 axis could be a novel therapeutic target for periodontal regeneration medicine.
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Zhao Z, Liu J, Weir MD, Schneider A, Ma T, Oates TW, Xu HHK, Zhang K, Bai Y. Periodontal ligament stem cell-based bioactive constructs for bone tissue engineering. Front Bioeng Biotechnol 2022; 10:1071472. [PMID: 36532583 PMCID: PMC9755356 DOI: 10.3389/fbioe.2022.1071472] [Citation(s) in RCA: 16] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/16/2022] [Accepted: 11/17/2022] [Indexed: 09/29/2023] Open
Abstract
Objectives: Stem cell-based tissue engineering approaches are promising for bone repair and regeneration. Periodontal ligament stem cells (PDLSCs) are a promising cell source for tissue engineering, especially for maxillofacial bone and periodontal regeneration. Many studies have shown potent results via PDLSCs in bone regeneration. In this review, we describe recent cutting-edge researches on PDLSC-based bone regeneration and periodontal tissue regeneration. Data and sources: An extensive search of the literature for papers related to PDLSCs-based bioactive constructs for bone tissue engineering was made on the databases of PubMed, Medline and Google Scholar. The papers were selected by three independent calibrated reviewers. Results: Multiple types of materials and scaffolds have been combined with PDLSCs, involving xeno genic bone graft, calcium phosphate materials and polymers. These PDLSC-based constructs exhibit the potential for bone and periodontal tissue regeneration. In addition, various osteo inductive agents and strategies have been applied with PDLSCs, including drugs, biologics, gene therapy, physical stimulation, scaffold modification, cell sheets and co-culture. Conclusoin: This review article demonstrates the great potential of PDLSCs-based bioactive constructs as a promising approach for bone and periodontal tissue regeneration.
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Affiliation(s)
- Zeqing Zhao
- Department of Orthodontics, School of Stomatology, Capital Medical University, Beijing, China
| | - Jin Liu
- Key Laboratory of Shaanxi Province for Craniofacial Precision Medicine Research, College of Stomatology, Xi’an Jiaotong University, Xi’an, China
| | - Michael D. Weir
- Biomaterials and Tissue Engineering Division, Department of Advanced Oral Sciences and Therapeutics, University of Maryland Dental School, Baltimore, MD, United States
| | - Abraham Schneider
- Department of Oncology and Diagnostic Sciences, University of Maryland School of Dentistry, Baltimore, MD, United States
| | - Tao Ma
- Department of Oncology and Diagnostic Sciences, University of Maryland School of Dentistry, Baltimore, MD, United States
| | - Thomas W. Oates
- Biomaterials and Tissue Engineering Division, Department of Advanced Oral Sciences and Therapeutics, University of Maryland Dental School, Baltimore, MD, United States
| | - Hockin H. K. Xu
- Biomaterials and Tissue Engineering Division, Department of Advanced Oral Sciences and Therapeutics, University of Maryland Dental School, Baltimore, MD, United States
- Marlene and Stewart Greenebaum Cancer Center, University of Maryland School of Medicine, Baltimore, MD, United States
- Center for Stem Cell Biology and Regenerative Medicine, University of Maryland School of Medicine, Baltimore, MD, United States
| | - Ke Zhang
- Department of Orthodontics, School of Stomatology, Capital Medical University, Beijing, China
| | - Yuxing Bai
- Department of Orthodontics, School of Stomatology, Capital Medical University, Beijing, China
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The role of noncoding RNAs in the osteogenic differentiation of human periodontal ligament-derived cells. Noncoding RNA Res 2022; 8:89-95. [DOI: 10.1016/j.ncrna.2022.11.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/13/2022] [Revised: 11/12/2022] [Accepted: 11/12/2022] [Indexed: 11/16/2022] Open
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Zhong X, Wang H. circSKIL promotes osteoblastic differentiation of periodontal ligament cells by sponging miR-532-5p to activate Notch signaling. J Periodontal Res 2022; 57:1148-1158. [PMID: 36063416 DOI: 10.1111/jre.13052] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/21/2022] [Revised: 08/08/2022] [Accepted: 08/24/2022] [Indexed: 12/09/2022]
Abstract
BACKGROUND AND OBJECTIVE Periodontal ligament cells (PDLCs) possess the capacity to differentiate into a variety of cell types to benefit periodontal regeneration. In this study, we examined the circSKIL/miR-532-5p/Notch1 axis in controlling the osteoblastic differentiation of PDLCs. METHODS Primary human PDLCs (hPDLCs) were isolated and induced to differentiate into osteoblasts. Osteogenic responses were assessed for the expressions of osteoblast-related marker proteins (including alkaline phosphatase (ALP), osteocalcin (OCN), bone morphogenetic protein-2 (BMP2), and runt-related transcription factor 2 (RUNX2) by RT-PCR. The formation of mineralized nodules was examined by Alizarin Red S (ARS) staining and ALP activity. Expressions of circSKIL, miR-532-5p, and Notch1 were measured by RT-PCR and western blotting, and their regulations by combining bioinformatic analysis and luciferase reporter assay. Notch signaling was assessed for the expressions of hairy and enhancer of split-1 (HES1) and Notch intracellular domain (NICD). RESULTS During osteoblastic differentiation of hPDLCs, circSKIL, and Notch1 were up-regulated, while miR-532-5p down-regulated. By sponging miR-532-5p, circSKIL activated Notch signaling, increasing levels of Notch1, HES1, and NICD. Functionally, knocking down circSKIL or overexpressing miR-532-5p inhibited osteoblastic differentiation of PDLCs, down-regulating ALP, OCN, BMP2, and RUNX2, and reducing ARS staining or ALP activity. The impacts of circSKIL knockdown were rescued by miR-532-5p inhibitor or overexpressing Notch1, while those caused by up-regulating miR-532-5p were reversed by overexpressing Notch1. CONCLUSION By targeting miR-532-5p and up-regulating Notch1, circSKIL critically controls osteoblastic differentiation of hPDLCs. Therefore, modulating this axis may maximize the differentiation of PDLCs into osteoblasts and benefit periodontal regeneration.
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Affiliation(s)
- Xiaohuan Zhong
- Center of Stomatology, Xiangya Hospital, Central South University, Changsha, China
| | - Huixin Wang
- Center of Stomatology, Xiangya Hospital, Central South University, Changsha, China
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Liu T, Huang T, Shang M, Han G. CircRNA ITCH: Insight Into Its Role and Clinical Application Prospect in Tumor and Non-Tumor Diseases. Front Genet 2022; 13:927541. [PMID: 35910224 PMCID: PMC9335290 DOI: 10.3389/fgene.2022.927541] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/24/2022] [Accepted: 06/21/2022] [Indexed: 11/13/2022] Open
Abstract
CircRNA E3 ubiquitin protein ligase (ITCH) (circRNA ITCH, circ-ITCH), a stable closed-loop RNA derived from the 20q11.22 region of chromosome 20, is a new circRNA discovered in the cytoplasm in recent decades. Studies have shown that it does not encode proteins, but regulates proteins expression at different levels. It is down-regulated in tumor diseases and is involved in a number of biological activities, including inhibiting cell proliferation, migration, invasion, and promoting apoptosis. It can also alter disease progression in non-tumor disease by affecting the cell cycle, inflammatory response, and critical proteins. Circ-ITCH also holds a lot of promise in terms of tumor and non-tumor clinical diagnosis, prognosis, and targeted therapy. As a result, in order to aid clinical research in the hunt for a new strategy for diagnosing and treating human diseases, this study describes the mechanism of circ-ITCH as well as its clinical implications.
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Affiliation(s)
- Tong Liu
- Department of Gastrointestinal Nutrition and Hernia Surgery, The Second Hospital of Jilin University, Changchun, China
| | - Tao Huang
- Department of Gastrointestinal Nutrition and Hernia Surgery, The Second Hospital of Jilin University, Changchun, China
| | - Mei Shang
- Department of Gastrointestinal Nutrition and Hernia Surgery, The Second Hospital of Jilin University, Changchun, China
| | - Gang Han
- Department of Gastrointestinal Nutrition and Hernia Surgery, The Second Hospital of Jilin University, Changchun, China
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ANGPTL4 regulates the osteogenic differentiation of periodontal ligament stem cells. Funct Integr Genomics 2022; 22:769-781. [PMID: 35831768 DOI: 10.1007/s10142-022-00882-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/19/2022] [Revised: 07/04/2022] [Accepted: 07/05/2022] [Indexed: 11/04/2022]
Abstract
The molecular mechanism of mechanical force regulating the osteogenic differentiation of periodontal ligament stem cells (PDLSCs) has not been clearly elucidated. In this study, two mRNA-seqs, GSE106887 and GSE109167, which contained several samples of PDLSCs under mechanical force, were downloaded from Gene Expression Omnibus. Differential expression analysis was firstly taken between GSE106887 and GSE109167, then the common 84 up-regulated genes and 26 down-regulated genes were selected. Function enrichment analysis was used to identify the key genes and pathways in PDLSCs subjected to the tension and compression force. PDLSCs were isolated from human periodontal ligament tissues. The effects of ANGPTL4 knockdown with shRNA on the osteogenic differentiation of PDLSCs were studied in vitro. Then, the orthodontic tooth movement (OTM) rat model was used to study the expression of HIF-1α and ANGPTL4 in alveolar bone remodeling in vivo. ANGPTL4 and the HIF-1 pathway were identified in PDLSCs subjected to the tension and compression force. alizarin red staining, alcian blue staining, and oil red O staining verified that PDLSCs had the ability of osteogenic, chondrogenic, and adipogenic differentiation, respectively. Verification experiment revealed that the expression of ANGPTL4 in PDLSCs significantly increased when cultured under osteogenic medium in vitro. While ANGPTL4 was knocked down by shRNA, the levels of ALPL, RUNX2, and OCN decreased significantly, as well as the protein levels of COL1A1, ALPL, RUNX2, and OCN. During the OTM, the expression of HIF-1α and ANGPTL4 in periodontal ligament cells increased on the tension and compression sides. We concluded the positive relationship between ANGPTL4 and osteogenic differentiation of PDLSCs.
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Chen X, Xie W, Zhang M, Shi Y, Xu S, Cheng H, Wu L, Pathak JL, Zheng Z. The Emerging Role of Non-Coding RNAs in Osteogenic Differentiation of Human Bone Marrow Mesenchymal Stem Cells. Front Cell Dev Biol 2022; 10:903278. [PMID: 35652090 PMCID: PMC9150698 DOI: 10.3389/fcell.2022.903278] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/24/2022] [Accepted: 04/25/2022] [Indexed: 11/13/2022] Open
Abstract
Autologous bone marrow-derived mesenchymal stem cells (BMSCs) are more easily available and frequently used for bone regeneration in clinics. Osteogenic differentiation of BMSCs involves complex regulatory networks affecting bone formation phenomena. Non-coding RNAs (ncRNAs) refer to RNAs that do not encode proteins, mainly including microRNAs, long non-coding RNAs, circular RNAs, piwi-interacting RNAs, transfer RNA-derived small RNAs, etc. Recent in vitro and in vivo studies had revealed the regulatory role of ncRNAs in osteogenic differentiation of BMSCs. NcRNAs had both stimulatory and inhibitory effects on osteogenic differentiation of BMSCs. During the physiological condition, osteo-stimulatory ncRNAs are upregulated and osteo-inhibitory ncRNAs are downregulated. The opposite effects might occur during bone degenerative disease conditions. Intracellular ncRNAs and ncRNAs from neighboring cells delivered via exosomes participate in the regulatory process of osteogenic differentiation of BMSCs. In this review, we summarize the recent advances in the regulatory role of ncRNAs on osteogenic differentiation of BMSCs during physiological and pathological conditions. We also discuss the prospects of the application of modulation of ncRNAs function in BMSCs to promote bone tissue regeneration in clinics.
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Affiliation(s)
- Xiaoying Chen
- Affiliated Stomatology Hospital of Guangzhou Medical University, Guangdong Engineering Research Center of Oral Restoration and Reconstruction, Guangzhou Key Laboratory of Basic and Applied Research of Oral Regenerative Medicine, Guangzhou, China
| | - Wei Xie
- Affiliated Stomatology Hospital of Guangzhou Medical University, Guangdong Engineering Research Center of Oral Restoration and Reconstruction, Guangzhou Key Laboratory of Basic and Applied Research of Oral Regenerative Medicine, Guangzhou, China
| | - Ming Zhang
- Affiliated Stomatology Hospital of Guangzhou Medical University, Guangdong Engineering Research Center of Oral Restoration and Reconstruction, Guangzhou Key Laboratory of Basic and Applied Research of Oral Regenerative Medicine, Guangzhou, China
| | - Yuhan Shi
- Affiliated Stomatology Hospital of Guangzhou Medical University, Guangdong Engineering Research Center of Oral Restoration and Reconstruction, Guangzhou Key Laboratory of Basic and Applied Research of Oral Regenerative Medicine, Guangzhou, China
| | - Shaofen Xu
- Affiliated Stomatology Hospital of Guangzhou Medical University, Guangdong Engineering Research Center of Oral Restoration and Reconstruction, Guangzhou Key Laboratory of Basic and Applied Research of Oral Regenerative Medicine, Guangzhou, China
| | - Haoyu Cheng
- Affiliated Stomatology Hospital of Guangzhou Medical University, Guangdong Engineering Research Center of Oral Restoration and Reconstruction, Guangzhou Key Laboratory of Basic and Applied Research of Oral Regenerative Medicine, Guangzhou, China
| | - Lihong Wu
- Affiliated Stomatology Hospital of Guangzhou Medical University, Guangdong Engineering Research Center of Oral Restoration and Reconstruction, Guangzhou Key Laboratory of Basic and Applied Research of Oral Regenerative Medicine, Guangzhou, China.,Department of Basic Oral Medicine, School and Hospital of Stomatology, Guangzhou Medical University, Guangzhou, China
| | - Janak L Pathak
- Affiliated Stomatology Hospital of Guangzhou Medical University, Guangdong Engineering Research Center of Oral Restoration and Reconstruction, Guangzhou Key Laboratory of Basic and Applied Research of Oral Regenerative Medicine, Guangzhou, China.,Department of Basic Oral Medicine, School and Hospital of Stomatology, Guangzhou Medical University, Guangzhou, China
| | - Zhichao Zheng
- Affiliated Stomatology Hospital of Guangzhou Medical University, Guangdong Engineering Research Center of Oral Restoration and Reconstruction, Guangzhou Key Laboratory of Basic and Applied Research of Oral Regenerative Medicine, Guangzhou, China.,Department of Basic Oral Medicine, School and Hospital of Stomatology, Guangzhou Medical University, Guangzhou, China.,Laboratory for Myology, Department of Human Movement Sciences, Faculty of Behavioural and Movement Sciences, Amsterdam Movement Sciences, Vrije Universiteit Amsterdam, Amsterdam, Netherlands
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GEO Database Screening Combined with In Vitro Experiments to Study the Mechanism of hsa_circ_0003570 in Infantile Hemangiomas. COMPUTATIONAL AND MATHEMATICAL METHODS IN MEDICINE 2022; 2022:5643742. [PMID: 35529258 PMCID: PMC9071871 DOI: 10.1155/2022/5643742] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/17/2022] [Accepted: 03/31/2022] [Indexed: 12/05/2022]
Abstract
Objective In this study, we screened out a type of differentially expressed circular RNA in infantile hemangioma (IH) cells and analyzed the mechanism in the malignant biological behavior of IH. Methods Based on the GSE98795, GSE100682, and GSE43742 datasets, differential expression analysis of circRNAs, microRNAs, and mRNAs was performed. The relative expression level of RNA was detected by quantitative real-time polymerase chain reaction (qRT-PCR). MTT assay, Transwell, flow cytometry analysis, and western blot were used to study the effects of hsa_circ_0003570, hsa-miR-138-5p, and RGS5 on the proliferation and apoptosis of hemangioma endothelial cells (HEMECs). Results The hsa_circ_0003570 and RGS5 mRNA were upregulated in HEMECs, but hsa-miR-138-5p was downregulated. Silencing of hsa_circ_0003570 inhibited the proliferation of HEMECs and promoted the apoptosis of HEMECs. The malignant biological behaviors of hsa_circ_0003570 on the proliferation and apoptosis of HEMECs were reversed by hsa-miR-138-5p. Hsa_circ_0003570 acted as the ceRNA of hsa-miR-138-5p and upregulated the expression of RGS5. Silencing of RGS5 inhibited the proliferation, migration, and invasion of HEMECs and promoted apoptosis. Conclusion Hsa_circ_0003570 promotes IH cell proliferation and inhibits IH cell apoptosis through hsa-miR-138-5p/RGS5 axis.
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Zhao C, Xie W, Zhu H, Zhao M, Liu W, Wu Z, Wang L, Zhu B, Li S, Zhou Y, Jiang X, Xu Q, Ren C. LncRNAs and their RBPs: How to influence the fate of stem cells? Stem Cell Res Ther 2022; 13:175. [PMID: 35505438 PMCID: PMC9066789 DOI: 10.1186/s13287-022-02851-x] [Citation(s) in RCA: 17] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2021] [Accepted: 04/12/2022] [Indexed: 12/12/2022] Open
Abstract
Stem cells are distinctive cells that have self-renewal potential and unique ability to differentiate into multiple functional cells. Stem cell is a frontier field of life science research and has always been a hot spot in biomedical research. Recent studies have shown that long non-coding RNAs (lncRNAs) have irreplaceable roles in stem cell self-renewal and differentiation. LncRNAs play crucial roles in stem cells through a variety of regulatory mechanisms, including the recruitment of RNA-binding proteins (RBPs) to affect the stability of their mRNAs or the expression of downstream genes. RBPs interact with different RNAs to regulate gene expression at transcriptional and post-transcriptional levels and play important roles in determining the fate of stem cells. In this review, the functions of lncRNAs and their RBPs in self-renewal and differentiation of stem cell are summarized. We focus on the four regulatory mechanisms by which lncRNAs and their RBPs are involved in epigenetic regulation, signaling pathway regulation, splicing, mRNA stability and subcellular localization and further discuss other noncoding RNAs (ncRNAs) and their RBPs in the fate of stem cells. This work provides a more comprehensive understanding of the roles of lncRNAs in determining the fate of stem cells, and a further understanding of their regulatory mechanisms will provide a theoretical basis for the development of clinical regenerative medicine.
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Affiliation(s)
- Cong Zhao
- Cancer Research Institute, Department of Neurosurgery, National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, 410008, China.,The Key Laboratory of Carcinogenesis of the Chinese Ministry of Health and the Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education, School of Basic Medicine, Central South University, Changsha, 410008, China
| | - Wen Xie
- Cancer Research Institute, Department of Neurosurgery, National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, 410008, China.,The Key Laboratory of Carcinogenesis of the Chinese Ministry of Health and the Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education, School of Basic Medicine, Central South University, Changsha, 410008, China
| | - Hecheng Zhu
- Changsha Kexin Cancer Hospital, Changsha, 410205, China
| | - Ming Zhao
- Changsha Kexin Cancer Hospital, Changsha, 410205, China
| | - Weidong Liu
- Cancer Research Institute, Department of Neurosurgery, National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, 410008, China.,The Key Laboratory of Carcinogenesis of the Chinese Ministry of Health and the Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education, School of Basic Medicine, Central South University, Changsha, 410008, China
| | - Zhaoping Wu
- Cancer Research Institute, Department of Neurosurgery, National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, 410008, China.,Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, 410008, China
| | - Lei Wang
- Cancer Research Institute, Department of Neurosurgery, National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, 410008, China.,The Key Laboratory of Carcinogenesis of the Chinese Ministry of Health and the Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education, School of Basic Medicine, Central South University, Changsha, 410008, China
| | - Bin Zhu
- Cancer Research Institute, Department of Neurosurgery, National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, 410008, China.,The Key Laboratory of Carcinogenesis of the Chinese Ministry of Health and the Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education, School of Basic Medicine, Central South University, Changsha, 410008, China
| | - Shasha Li
- Cancer Research Institute, Department of Neurosurgery, National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, 410008, China.,The Key Laboratory of Carcinogenesis of the Chinese Ministry of Health and the Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education, School of Basic Medicine, Central South University, Changsha, 410008, China
| | - Yao Zhou
- Cancer Research Institute, Department of Neurosurgery, National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, 410008, China.,The Key Laboratory of Carcinogenesis of the Chinese Ministry of Health and the Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education, School of Basic Medicine, Central South University, Changsha, 410008, China
| | - Xingjun Jiang
- Cancer Research Institute, Department of Neurosurgery, National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, 410008, China. .,Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, 410008, China.
| | - Qiang Xu
- Department of Orthopedics, The Affiliated Zhuzhou Hospital of Xiangya Medical College, Central South University, Zhuzhou, 412007, China. .,School of Materials Science and Engineering, Central South University, Changsha, 410083, China.
| | - Caiping Ren
- Cancer Research Institute, Department of Neurosurgery, National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, 410008, China. .,The Key Laboratory of Carcinogenesis of the Chinese Ministry of Health and the Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education, School of Basic Medicine, Central South University, Changsha, 410008, China.
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Abstract
Circular RNAs (circRNAs) are a novel class of noncoding RNAs that widely exist in eukaryotes. As a new focus in the field of molecular regulation, circRNAs have attracted much attention in recent years. Previous studies have confirmed that circRNAs are associated with many physiological and pathological processes. CircRNAs also participate in the regulation of stem cells. Stem cells have the properties of self-renewal and differentiation, which make stem cell therapy popular. CircRNAs may serve as new targets in stem cell therapy due to their regulation in stem cells. However, the underlying relationships between circRNAs and stem cells are still being explored. In this review, we briefly summarize the effects of circRNAs on stem cells, in the context of biological activities, aging and apoptosis, and aberrant changes. Moreover, we also examine the biological roles of stem cell-derived exosomal circRNAs. We believe our review will provide insights into the effects of circRNAs on stem cells.
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Zeng B, Huang J. Progress in the Study of Non-Coding RNAs in Multidifferentiation Potential of Dental-Derived Mesenchymal Stem Cells. Front Genet 2022; 13:854285. [PMID: 35480302 PMCID: PMC9037064 DOI: 10.3389/fgene.2022.854285] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2022] [Accepted: 03/17/2022] [Indexed: 12/28/2022] Open
Abstract
For decades, the desire for tissue regeneration has never been quenched. Dental-derived mesenchymal stem cells (DMSCs), with the potential of self-renewal and multi-directional differentiation, have attracted much attention in this topic. Growing evidence suggests that non-coding RNAs (ncRNAs) can activate various regulatory processes. Even with a slight decrease or increase in expression, ncRNAs can weaken or even subvert cellular fate. Therefore, a systematic interpretation of ncRNAs that guide the differentiation of DMSCs into cells of other tissue types is urgently needed. In this review, we introduce the roles of ncRNAs in the differentiation of DMSCs, such as osteogenic differentiation, odontogenic differentiation, neurogenic differentiation, angiogenic differentiation and myogenic differentiation. Additionally, we illustrate the regulatory mechanisms of ncRNAs in the differentiation of DMSCs, such as epigenetic regulation, transcriptional regulation, mRNA modulation, miRNA sponges and signalling. Finally, we summarize the types and mechanisms of ncRNAs in the differentiation of DMSCs, such as let-7 family, miR-17∼92 family, miR-21, lncRNA H19, lncRNA ANCR, lncRNA MEG3, circRNA CDR1as and CircRNA SIPA1L1. If revealing the intricate relationship between ncRNAs and pluripotency of DMSCs 1 day, the application of DMSCs in regenerative medicine and tissue engineering will be improved. Our work could be an important stepping stone towards this future.
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Affiliation(s)
- Biyun Zeng
- Department of Oral Pathology, Xiangya Stomatological Hospital & Hunan Key Laboratory of Oral Health Research & Hunan 3D Printing Engineering Research Center of Oral Care, Central South University, Changsha, China
| | - Junhui Huang
- Department of Oral Pathology, Xiangya Stomatological Hospital & Hunan Key Laboratory of Oral Health Research & Hunan 3D Printing Engineering Research Center of Oral Care, Central South University, Changsha, China
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40
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Wang K, Li M, Duan H, Zhang T, Xu C, Yu F. SLCO4A1‐AS1 triggers the malignant behaviors of melanoma cells via sponging miR‐1306‐5p to enhance PCGF2. Exp Dermatol 2022; 31:1220-1233. [PMID: 35427425 DOI: 10.1111/exd.14577] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/08/2020] [Revised: 03/18/2022] [Accepted: 04/12/2022] [Indexed: 11/27/2022]
Affiliation(s)
- Kai Wang
- Henan Provincial People’s Hospital International Medical Center Department of Plastic Surgery Zhengzhou University People’s Hospital Henan University People’s Hospital Zhengzhou 450003 Henan China
| | - Min Li
- Department of Dermatology Henan Provincial People’s Hospital Zhengzhou University People’s Hospital Henan University People’s Hospital Zhengzhou 450003 Henan China
| | - Hongyan Duan
- Henan Provincial People’s Hospital International Medical Center Zhengzhou University People’s Hospital Henan University People’s Hospital Zhengzhou 450003 Henan China
| | - Tong Zhang
- Henan Provincial People’s Hospital International Medical Center Zhengzhou University People’s Hospital Henan University People’s Hospital Zhengzhou 450003 Henan China
| | - Chengyang Xu
- Henan Provincial People’s Hospital International Medical Center Zhengzhou University People’s Hospital Henan University People’s Hospital Zhengzhou 450003 Henan China
| | - Feifei Yu
- Henan Provincial People’s Hospital International Medical Center Zhengzhou University People’s Hospital Henan University People’s Hospital Zhengzhou 450003 Henan China
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Ma L, Zhang M, Cao F, Han J, Han P, Wu Y, Deng R, Zhang G, An X, Zhang L, Song Y, Cao B. Effect of MiR-100-5p on proliferation and apoptosis of goat endometrial stromal cell in vitro and embryo implantation in vivo. J Cell Mol Med 2022; 26:2543-2556. [PMID: 35411593 PMCID: PMC9077292 DOI: 10.1111/jcmm.17226] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/18/2021] [Revised: 01/05/2022] [Accepted: 01/10/2022] [Indexed: 12/13/2022] Open
Abstract
The growth of endometrial stromal cells (ESCs) at implantation sites may be a potential factor affecting the success rate of embryo implantation. Incremental proofs demonstrated that ncRNAs (e.g. miRNAs, lncRNAs and circRNAs) were involved in various biological procedures, including proliferation and apoptosis. In this study, the role of miR‐100‐5p on proliferation and apoptosis of goat ESCs in vitro and embryo implantation in vivo was determined. The mRNA expression of miR‐100‐5p was significantly inhibited in the receptive phase (RE) rather than in the pre‐receptive phase (PE). Overexpression of miR‐100‐5p suppressed ESCs proliferation and induced apoptosis. The molecular target of MiR‐100‐5p, HOXA1, was confirmed by 3′‐UTR assays. Meanwhile, the product of HOXA1 mRNA RT‐PCR increased in the RE more than that in the PE. The HOXA1‐siRNA exerted significant negative effects on growth arrest. Instead, incubation of ESCs with miR‐100‐5p inhibitor or overexpressed HOXA1 promoted the cell proliferation. In addition, Circ‐9110 which acted as a sponge for miR‐100‐5p reversed the relevant biological effects of miR‐100‐5p. The intrinsic apoptosis pathway was suppressed in ESCs, revealing a crosstalk between Circ‐9110/miR‐100‐5p/HOXA1 axis, PI3K/AKT/mTOR, and ERK1/2 pathways. To further evaluate the progress in study on embryo implantation regulating mechanism of miR‐100‐5p in vivo, the pinopodes of two phases were observed and analysed, suggesting that, as similar as in situ, miR‐100‐5p was involved in significantly regulating embryo implantation in vivo. Mechanistically, miR‐100‐5p performed its embryo implantation function through regulation of PI3K/AKT/mTOR and ERK1/2 pathways by targeting Circ‐9110/miR‐100‐5p/HOXA1 axis in vivo.
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Affiliation(s)
- Li Ma
- College of Animal Science and Technology, Northwest A&F University, Yangling, China.,Shaanxi University of Chinese Medicine, Xianyang, China
| | - Meng Zhang
- College of Animal Science and Technology, Northwest A&F University, Yangling, China
| | - Fangjun Cao
- College of Animal Science and Technology, Northwest A&F University, Yangling, China.,Shaanxi Institute of Zoology, Xi'an, China
| | - Jincheng Han
- College of Animal Science and Technology, Northwest A&F University, Yangling, China
| | - Peng Han
- College of Animal Science and Technology, Northwest A&F University, Yangling, China
| | - Yeting Wu
- College of Food Science and Engineering, Northwest A&F University, Yangling, China
| | - Renyi Deng
- Department of Foreign Languages, Northwest A&F University, Yangling, China
| | - Guanghui Zhang
- College of Innovation and Experiment, Northwest A&F University, Yangling, China
| | - Xiaopeng An
- College of Animal Science and Technology, Northwest A&F University, Yangling, China
| | - Lei Zhang
- College of Animal Science and Technology, Northwest A&F University, Yangling, China
| | - Yuxuan Song
- College of Animal Science and Technology, Northwest A&F University, Yangling, China
| | - Binyun Cao
- College of Animal Science and Technology, Northwest A&F University, Yangling, China
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42
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Wang C, Gong J, Li D, Xing X. circ_0062491 alleviates periodontitis via the miR-142-5p/IGF1 axis. Open Med (Wars) 2022; 17:638-647. [PMID: 35480399 PMCID: PMC8994215 DOI: 10.1515/med-2022-0442] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/05/2021] [Revised: 01/24/2022] [Accepted: 01/27/2022] [Indexed: 11/21/2022] Open
Abstract
CircularRNAs (circRNAs) are collectively involved in periodontitis. The aim of this study was to explore the roles of circ_0062491 in osteogenic differentiation of PDLSCs and provide a novel method for periodontitis treatment. mRNA and protein expression levels were measured by qRT-PCR and western blotting. Alkaline phosphatase (ALP) and alizarin red S (ARS) staining were used to detect the activity of osteogenesis. Furthermore, the interactions between miR-142-5p and circ_0062491/IGF1 were verified by a luciferase reporter assay. circ_0062491 was suppressed in PDL tissues of periodontitis patients and overexpressed in osteogenesis-induced PDLSCs. Upregulated circ_0062491 promoted osteogenic differentiation of PDLSCs. miR-142-5p was verified to be a target of circ_0062491, and the overexpression of miR-142-5p suppressed the osteogenic differentiation of PDLSCs induced by circ_0062491 Additionally, miR-142-5p targeted IGF1, and silenced IGF1 abrogated the effects of suppressed miR-142-5p on osteogenic differentiation of PDLSCs. In conclusion, circ_0062491 acted as a competing endogenous RNA to regulate osteogenic differentiation of PDLSCs via the miR-142-5p/IGF1 axis.
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Affiliation(s)
- Chunlin Wang
- Department of Pediatric Dentistry, Nanjing Stomatological Hospital, Medical School of Nanjing University, Xuanwu District, Nanjing, Jiangsu 210000, China
| | - Junxia Gong
- Department of First Outpatient, Nanjing Stomatological Hospital, Medical School of Nanjing University, Nanjing, China
| | - Dai Li
- Department of Pediatric Dentistry, Nanjing Stomatological Hospital, Medical School of Nanjing University, Xuanwu District, Nanjing, Jiangsu 210000, China
| | - Xianghui Xing
- Department of Pediatric Dentistry, Nanjing Stomatological Hospital, Medical School of Nanjing University, Xuanwu District, Nanjing, Jiangsu 210000, China
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43
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Yu W, Gu Q, Wu D, Zhang W, Li G, Lin L, Lowe JM, Hu S, Li TW, Zhou Z, Miao MZ, Gong Y, Zhao Y, Lu E. Identification of potentially functional circRNAs and prediction of circRNA-miRNA-mRNA regulatory network in periodontitis: Bridging the gap between bioinformatics and clinical needs. J Periodontal Res 2022; 57:594-614. [PMID: 35388494 PMCID: PMC9325354 DOI: 10.1111/jre.12989] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/22/2021] [Revised: 03/19/2022] [Accepted: 03/23/2022] [Indexed: 02/06/2023]
Abstract
Background and Objective Periodontitis is a multifactorial chronic inflammatory disease that can lead to the irreversible destruction of dental support tissues. As an epigenetic factor, the expression of circRNA is tissue‐dependent and disease‐dependent. This study aimed to identify novel periodontitis‐associated circRNAs and predict relevant circRNA‐periodontitis regulatory network by using recently developed bioinformatic tools and integrating sequencing profiling with clinical information for getting a better and more thorough image of periodontitis pathogenesis, from gene to clinic. Material and Methods High‐throughput sequencing and RT‐qPCR were conducted to identify differentially expressed circRNAs in gingival tissues from periodontitis patients. The relationship between upregulated circRNAs expression and probing depth (PD) was performed using Spearman's correlation analysis. Bioinformatic analyses including GO analysis, circRNA‐disease association prediction, and circRNA‐miRNA‐mRNA network prediction were performed to clarify potential regulatory functions of identified circRNAs in periodontitis. A receiver‐operating characteristic (ROC) curve was established to assess the diagnostic significance of identified circRNAs. Results High‐throughput sequencing identified 70 differentially expressed circRNAs (68 upregulated and 2 downregulated circRNAs) in human periodontitis (fold change >2.0 and p < .05). The top five upregulated circRNAs were validated by RT‐qPCR that had strong associations with multiple human diseases, including periodontitis. The upregulation of circRNAs were positively correlated with PD (R = .40–.69, p < .05, moderate). A circRNA‐miRNA‐mRNA network with the top five upregulated circRNAs, differentially expressed mRNAs, and overlapped predicted miRNAs indicated potential roles of circRNAs in immune response, cell apoptosis, migration, adhesion, and reaction to oxidative stress. The ROC curve showed that circRNAs had potential value in periodontitis diagnosis (AUC = 0.7321–0.8667, p < .05). Conclusion CircRNA‐disease associations were predicted by online bioinformatic tools. Positive correlation between upregulated circRNAs, circPTP4A2, chr22:23101560‐23135351+, circARHGEF28, circBARD1 and circRASA2, and PD suggested function of circRNAs in periodontitis. Network prediction further focused on downstream targets regulated by circRNAs during periodontitis pathogenesis.
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Affiliation(s)
- Weijun Yu
- Department of Stomatology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.,College of Stomatology, Shanghai Jiao Tong University, Shanghai, China
| | - Qisheng Gu
- Key Laboratory of Molecular Virology and Immunology, Institut Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai, China.,Department of Immunology, Bio Sorbonne Paris Cité, University of Paris, Paris, France
| | - Di Wu
- Division of Oral and Craniofacial Biomedicine, University of North Carolina Adams School of Dentistry, Chapel Hill, North Carolina, USA.,Department of Biostatistics, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA
| | - Weiqi Zhang
- Department of Stomatology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Gang Li
- Department of Genome Sciences, University of Washington, Seattle, Washington, USA
| | - Lu Lin
- Department of Stomatology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Jared M Lowe
- Department of Chemistry, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA
| | - Shucheng Hu
- Department of Stomatology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Tia Wenjun Li
- Division of Oral and Craniofacial Biomedicine, University of North Carolina Adams School of Dentistry, Chapel Hill, North Carolina, USA.,Gene Therapy Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA
| | - Zhen Zhou
- Center for Biomedical Image Computing and Analytics, Department of Radiology, University of Pennsylvania, Philadelphia, Pennsylvania, USA
| | - Michael Z Miao
- Division of Oral and Craniofacial Biomedicine, University of North Carolina Adams School of Dentistry, Chapel Hill, North Carolina, USA
| | - Yuhua Gong
- Department of Stomatology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Yifei Zhao
- Department of Stomatology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Eryi Lu
- Department of Stomatology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.,College of Stomatology, Shanghai Jiao Tong University, Shanghai, China
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Circular RNA ITCH: An Emerging Multifunctional Regulator. Biomolecules 2022; 12:biom12030359. [PMID: 35327551 PMCID: PMC8944968 DOI: 10.3390/biom12030359] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/06/2022] [Revised: 02/21/2022] [Accepted: 02/22/2022] [Indexed: 12/28/2022] Open
Abstract
In the last decade, numerous circRNAs were discovered by virtue of the RNA-Seq technique. With the deepening of experimental research, circRNAs have brought to light the key biological functions and progression of human diseases. CircRNA ITCH has been demonstrated to be a tumor suppressor in numerous cancers, and recently it was found to play an important role in bone diseases, diabetes mellitus, and cardiovascular diseases. However, the functions of circ-ITCH have not been completely understood. In this review, we comprehensively provide a conceptual framework to elucidate circ-ITCH biological functions of cell proliferation, apoptosis and differentiation, and the pathological mechanisms of inflammation, drug resistance/toxicity, and tumorigenesis. Finally, we summarize its clinical applications in various diseases. This research aimed at clarifying the role of circ-ITCH, which could be a promising therapeutic target.
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45
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Kang Y, Pei W. Transcriptomic analysis and biological evaluation reveals that LMO3 regulates the osteogenic differentiation of human adipose derived stem cells via PI3K/Akt signaling pathway. J Mol Histol 2022; 53:379-394. [PMID: 35165791 DOI: 10.1007/s10735-021-10047-5] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2021] [Accepted: 12/06/2021] [Indexed: 10/19/2022]
Abstract
Autologous bone transplantation which is a common treatment method for bone defects needs a large quantity of bone cells. In order to develop new treatments to regenerating bone tissues, this research aimed at identifying the key genes and finding their mechanism in human adipose-derived stem cells (hADSCs) osteogenesis. GSE63754, GSE89330 and GSE72429 were downloaded to perform GO functional and KEGG pathway analyses, construct a competing endogenous RNA (ceRNA) network, construct a PPI network and identify hub genes. The expression level of LMO3 during the osteogenesis of hADSCs was examined by quantitative reverse transcription polymerase chain reaction and western blot. Lentivirus transfection was used to knock down or overexpress LMO3, which enabled us to investigate the effect of LMO3 on osteogenic differentiation of hADSCs. Wortmannin were used to identify the mechanism of the LMO3/PI3K/Akt axis in regulating osteogenic differentiation of hADSCs. Moreover, ectopic bone formation in nude mice was used to investigate the effect of LMO3 on osteogenesis in vivo. In this study, we found the expression of LMO3 was significantly upregulated during the osteogenic differentiation of hADSCs. LMO3 knockdown remarkably suppressed osteogenic differentiation of hADSCs, while LMO3 overexpression promoted osteogenic differentiation of hADSCs both in vitro and in vivo. Moreover, we discovered that the enhancing effect of LMO3 overexpression on osteogenic differentiation was related to the activation of PI3K/Akt signaling pathway. Inhibition of PI3K/Akt signaling pathway with wortmannin effectively blocked the stimulation of osteogenic differentiation induced by LMO3 overexpression. In conclusion, based on transcriptomic analysis, we identified key genes involved in regulating the osteogenic differentiation of hADSCs. In addition, we found that LMO3 might act as a positive modulator of hADSC osteogenic differentiation by mediating PI3K/Akt signaling pathway. Manipulating the expression of LMO3 and its associated pathways might contribute to advances in bone regeneration and tissue engineering.
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Affiliation(s)
- Yue Kang
- Department of Breast Surgery, Cancer Hospital of China Medical University, No. 44 Xiaoheyan Road, Dadong District, Shenyang, 110042, Liaoning Province, People's Republic of China
| | - Wenye Pei
- Department of Information Management, Cancer Hospital of China Medical University, No. 44 Xiaoheyan Road, Dadong District, Shenyang, 110042, Liaoning Province, People's Republic of China.
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Lin Y, Tang Z, Jin L, Yang Y. The Expression and Regulatory Roles of Long Non-Coding RNAs in Periodontal Ligament Cells: A Systematic Review. Biomolecules 2022; 12:biom12020304. [PMID: 35204802 PMCID: PMC8869287 DOI: 10.3390/biom12020304] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/10/2022] [Revised: 02/07/2022] [Accepted: 02/09/2022] [Indexed: 02/08/2023] Open
Abstract
Periodontal ligament (PDL) cells play a pivotal role in periodontal and bone homeostasis and have promising potential for regenerative medicine and tissue engineering. There is compelling evidence that long non-coding RNAs (lncRNAs) are differentially expressed in PDL cells compared to other cell types and that these lncRNAs are involved in a variety of biological processes. This study systematically reviews the current evidence regarding the expression and regulatory functions of lncRNAs in PDL cells during various biological processes. A systematic search was conducted on PubMed, the Web of Science, Embase, and Google Scholar to include articles published up to 1 July 2021. Original research articles that investigated the expression or regulation of lncRNAs in PDL cells were selected and evaluated for a systematic review. Fifty studies were ultimately included, based on our eligibility criteria. Thirteen of these studies broadly explored the expression profiles of lncRNAs in PDL cells using microarray or RNA sequencing. Nineteen studies investigated the mechanisms by which lncRNAs regulate osteogenic differentiation in PDL cells. The remaining 18 studies investigated the mechanism by which lncRNAs regulate the responses of PDL cells to various stimuli, namely, lipopolysaccharide-induced inflammation, tumor necrosis factor alpha-induced inflammation, mechanical stress, oxidative stress, or hypoxia. We systematically reviewed studies on the expression and regulatory roles of lncRNAs in diverse biological processes in PDL cells, including osteogenic differentiation and cellular responses to inflammation, mechanical stress, and other stimuli. These results provide new insights that may guide the development of lncRNA-based therapeutics for periodontal and bone regeneration.
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Affiliation(s)
- Yifan Lin
- Division of Paediatric Dentistry and Orthodontics, Faculty of Dentistry, The University of Hong Kong, Hong Kong, China; (Y.L.); (Z.T.)
| | - Zhongyuan Tang
- Division of Paediatric Dentistry and Orthodontics, Faculty of Dentistry, The University of Hong Kong, Hong Kong, China; (Y.L.); (Z.T.)
| | - Lijian Jin
- Division of Periodontology and Implant Dentistry, Faculty of Dentistry, The University of Hong Kong, Hong Kong, China;
| | - Yanqi Yang
- Division of Paediatric Dentistry and Orthodontics, Faculty of Dentistry, The University of Hong Kong, Hong Kong, China; (Y.L.); (Z.T.)
- Correspondence:
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47
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Zhang Y, Zhang H, Yuan G, Yang G. circKLF4 Upregulates Klf4 and Endoglin to Promote Odontoblastic Differentiation of Mouse Dental Papilla Cells via Sponging miRNA-1895 and miRNA-5046. Front Physiol 2022; 12:760223. [PMID: 35222058 PMCID: PMC8865004 DOI: 10.3389/fphys.2021.760223] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/17/2021] [Accepted: 10/29/2021] [Indexed: 12/03/2022] Open
Abstract
circular RNAs (circRNAs) is a broad and diverse endogenous subfamily of non-coding RNAs, regulating the gene expression by acting as a microRNA (miRNA) sponge. However, the biological functions of circRNAs in odontoblast differentiation remain largely unknown. Our preliminary study identified an unknown mouse circRNA by circRNA sequencing generated from mouse dental papilla and we termed it circKLF4. In this study, quantitative real-time PCR and in situ hybridization were used and demonstrated that circKLF4 was upregulated during odontoblastic differentiation. Gene knockdown and overexpression assays indicated that circKLF4 promoted odontoblastic differentiation of mouse dental papilla cells (mDPCs). Mechanistically, we found that circKLF4 increased the linear KLF4 expression in a microRNA-dependent manner. By mutating the binding sites of microRNA and circKLF4, we further confirmed that circKLF4 acted as sponge of miRNA-1895 and miRNA-5046 to promote the expression of KLF4. We then also found that ENDOGLIN was also up-regulated by circKLF4 by transfection of circKLF4 overexpression plasmids with or without microRNA inhibitor. In conclusion, circKLF4 increases the expression of KLF4 and ENDOGLIN to promote odontoblastic differentiation via sponging miRNA-1895 and miRNA-5046.
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CircRNA hsa_circ_0001421 promotes the osteoblast differentiation of human adipose mesenchymal stem cells through the miR-608/SP7 axis. Biochem Eng J 2022. [DOI: 10.1016/j.bej.2022.108386] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/18/2022]
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49
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Li Y, Zhao X, Sun M, Pei D, Li A. Deciphering the Epigenetic Code of Stem Cells Derived From Dental Tissues. FRONTIERS IN DENTAL MEDICINE 2022. [DOI: 10.3389/fdmed.2021.807046] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
Abstract
Stem cells derived from dental tissues (DSCs) exhibit multipotent regenerative potential in pioneering tissue engineering regimens. The multipotency of DSCs is critically regulated by an intricate range of factors, of which the epigenetic influence is considered vital. To gain a better understanding of how epigenetic alterations are involved in the DSC fate determination, the present review overviews the current knowledge relating to DSC epigenetic modifications, paying special attention to the landscape of epigenetic modifying agents as well as the related signaling pathways in DSC regulation. In addition, insights into the future opportunities of epigenetic targeted therapies mediated by DSCs are discussed to hold promise for the novel therapeutic interventions in future translational medicine.
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50
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Li H, Zheng Q, Xie X, Wang J, Zhu H, Hu H, He H, Lu Q. Role of Exosomal Non-Coding RNAs in Bone-Related Diseases. Front Cell Dev Biol 2022; 9:811666. [PMID: 35004702 PMCID: PMC8733689 DOI: 10.3389/fcell.2021.811666] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/09/2021] [Accepted: 12/09/2021] [Indexed: 12/11/2022] Open
Abstract
Bone-related diseases seriously affect the lives of patients and carry a heavy economic burden on society. Treatment methods cannot meet the diverse clinical needs of affected patients. Exosomes participate in the occurrence and development of many diseases through intercellular communication, including bone-related diseases. Studies have shown that exosomes can take-up and “package” non-coding RNAs and “deliver” them to recipient cells, thereby regulating the function of recipient cells. The exosomal non-coding RNAs secreted by osteoblasts, osteoclasts, chondrocytes, and other cells are involved in the regulation of bone-related diseases by inhibiting osteoclasts, enhancing chondrocyte activity and promoting angiogenesis. Here, we summarize the role and therapeutic potential of exosomal non-coding RNAs in the bone-related diseases osteoporosis, osteoarthritis, and bone-fracture healing, and discuss the clinical application of exosomes in patients with bone-related diseases.
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Affiliation(s)
- Hang Li
- Department of Pharmacy, The Second Xiangya Hospital, Central South University, Changsha, China.,Institute of Clinical Pharmacy, Central South University, Changsha, China
| | - Qiyue Zheng
- Department of Pharmacy, The Second Xiangya Hospital, Central South University, Changsha, China.,Institute of Clinical Pharmacy, Central South University, Changsha, China
| | - Xinyan Xie
- Department of Pharmacy, The Second Xiangya Hospital, Central South University, Changsha, China.,Institute of Clinical Pharmacy, Central South University, Changsha, China.,College of Traditional Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Jiaojiao Wang
- Department of Pharmacy, The Second Xiangya Hospital, Central South University, Changsha, China.,Institute of Clinical Pharmacy, Central South University, Changsha, China
| | - Haihong Zhu
- Department of Pharmacy, The Second Xiangya Hospital, Central South University, Changsha, China.,Institute of Clinical Pharmacy, Central South University, Changsha, China
| | - Haoye Hu
- Department of Medical Genetics, The Second Xiangya Hospital, Central South University, Changsha, China
| | - Hao He
- Department of Vascular Surgery, The Second Xiangya Hospital of Central South University, Changsha, China
| | - Qiong Lu
- Department of Pharmacy, The Second Xiangya Hospital, Central South University, Changsha, China.,Institute of Clinical Pharmacy, Central South University, Changsha, China
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