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Huang L, Chen X, Yang X, Zhang Y, Liang Y, Qiu X. Elucidating epigenetic mechanisms governing odontogenic differentiation in dental pulp stem cells: an in-depth exploration. Front Cell Dev Biol 2024; 12:1394582. [PMID: 38863943 PMCID: PMC11165363 DOI: 10.3389/fcell.2024.1394582] [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: 03/01/2024] [Accepted: 05/13/2024] [Indexed: 06/13/2024] Open
Abstract
Epigenetics refers to the mechanisms such as DNA methylation and histone modification that influence gene expression without altering the DNA sequence. These epigenetic modifications can regulate gene transcription, splicing, and stability, thereby impacting cell differentiation, development, and disease occurrence. The formation of dentin is intrinsically linked to the odontogenic differentiation of dental pulp stem cells (DPSCs), which are recognized as the optimal cell source for dentin-pulp regeneration due to their varied odontogenic potential, strong proliferative and angiogenic characteristics, and ready accessibility Numerous studies have demonstrated the critical role of epigenetic regulation in DPSCs differentiation into specific cell types. This review thus provides a comprehensive review of the mechanisms by which epigenetic regulation controls the odontogenesis fate of DPSCs.
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Affiliation(s)
| | | | | | | | | | - Xiaoling Qiu
- Department of Endodontics, Stomatological Hospital, School of Stomatology, Southern Medical University, Guangzhou, Guangdong, China
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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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3
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Zhang Y, Chen X, Yang X, Huang L, Qiu X. Mesenchymal Stem Cell-Derived from Dental Tissues-Related lncRNAs: A New Regulator in Osteogenic Differentiation. J Tissue Eng Regen Med 2023; 2023:4622584. [PMID: 40226409 PMCID: PMC11919082 DOI: 10.1155/2023/4622584] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/13/2023] [Revised: 06/12/2023] [Accepted: 06/22/2023] [Indexed: 04/15/2025]
Abstract
Odontogenic stem cells are mesenchymal stem cells (MSCs) with multipotential differentiation potential from different dental tissues. Their osteogenic differentiation is of great significance in bone tissue engineering. In recent years, it has been found that long noncoding RNAs (lncRNAs) participate in regulating the osteoblastic differentiation of stem cells at the epigenetic level, transcriptional level, and posttranscriptional level. We reviewed the existing lncRNA related to the osteogenic differentiation of odontogenic stem cells and emphasized the critical mechanism of lncRNA in the osteogenic differentiation of odontogenic stem cells. These findings are expected to be an important target for promoting osteoblastic differentiation of odontogenic stem cells in bone regeneration therapy with lncRNA.
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Affiliation(s)
- Yinchun Zhang
- Department of Endodontics, Stomatological Hospital, School of Stomatology, Southern Medical University, Guangdong 510280, China
| | - Xuan Chen
- Department of Endodontics, Stomatological Hospital, School of Stomatology, Southern Medical University, Guangdong 510280, China
| | - XiaoXia Yang
- Department of Endodontics, Stomatological Hospital, School of Stomatology, Southern Medical University, Guangdong 510280, China
| | - Lei Huang
- Department of Endodontics, Stomatological Hospital, School of Stomatology, Southern Medical University, Guangdong 510280, China
| | - Xiaoling Qiu
- Department of Endodontics, Stomatological Hospital, School of Stomatology, Southern Medical University, Guangdong 510280, China
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Liu B, Zhang C, Zhao H, Gao J, Hu J. Chitosan Hydrogel-Delivered ABE8e Corrects PAX9 Mutant in Dental Pulp Stem Cells. Gels 2023; 9:436. [PMID: 37367107 DOI: 10.3390/gels9060436] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/25/2023] [Revised: 05/19/2023] [Accepted: 05/23/2023] [Indexed: 06/28/2023] Open
Abstract
Hypodontia (dental agenesis) is a genetic disorder, and it has been identified that the mutation C175T in PAX9 could lead to hypodontia. Cas9 nickase (nCas9)-mediated homology-directed repair (HDR) and base editing were used for the correction of this mutated point. This study aimed to investigate the effect of HDR and the base editor ABE8e in editing PAX9 mutant. It was found that the chitosan hydrogel was efficient in delivering naked DNA into dental pulp stem cells (DPSCs). To explore the influence of the C175T mutation in PAX9 on the proliferation of DPSCs, hydrogel was employed to deliver PAX9 mutant vector into DPSCs, finding that the PAX9-containing C175T mutation failed to promote the proliferation of DPSCs. Firstly, DPSCs stably carrying PAX9 mutant were constructed. Either an HDR or ABE8e system was delivered into the above-mentioned stable DPSCs, and then the correction efficiency using Sanger sequencing and Western blotting was determined. Meanwhile, the ABE8e presented significantly higher efficiency in correcting C175T compared with HDR. Furthermore, the corrected PAX9 presented enhanced viability and differentiation capacity for osteogenic and neurogenic lineages; the corrected PAX9 even possessed extremely enhanced transcriptional activation ability. In summary, this study has powerful implications for studies into base editors, chitosan hydrogel, and DPSCs in treating hypodontia.
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Affiliation(s)
- Bowen Liu
- Outpatient Department of Oral and Maxillofacial Surgery, Beijing Stomatological Hospital, School of Stomatology, Capital Medical University, Tian Tan Xi Li No. 4, Beijing 100050, China
| | - Chenjiao Zhang
- Department of General, Beijing Stomatological Hospital, School of Stomatology, Capital Medical University, Tian Tan Xi Li No. 4, Beijing 100050, China
| | - Han Zhao
- Multi-Disciplinary Treatment Center, Beijing Stomatological Hospital, School of Stomatology, Capital Medical University, Tian Tan Xi Li No. 4, Beijing 100050, China
| | - Jian Gao
- State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, China
| | - Jingchao Hu
- Department of Periodontics, Beijing Stomatological Hospital, School of Stomatology, Capital Medical University, Tian Tan Xi Li No. 4, Beijing 100050, China
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Zhu N, Wang D, Xie F, Qin M, Wang Y. MiR-335-3p/miR-155-5p Involved in IGFBP7-AS1-Enhanced Odontogenic Differentiation. Int Dent J 2022; 73:362-369. [PMID: 35999071 DOI: 10.1016/j.identj.2022.07.008] [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: 05/30/2022] [Revised: 07/03/2022] [Accepted: 07/18/2022] [Indexed: 11/15/2022] Open
Abstract
BACKGROUND The differentiation of stem cells from exfoliated deciduous teeth (SHEDs) into odontoblasts determines the regeneration of dentin-pulp complex. Non-coding RNAs (ncRNAs), including microRNA (miRNA) and long non-coding RNA (lncRNA), participate in many multiple biological processes, but the specific miRNAs involved in odontogenesis are incompletely defined. It was confirmed that lncRNA IGFBP7-AS1 could positively regulate odontogenetic differentiation in SHEDs. To investigate the downstream mechanisms of this process, miR-335-3p and miR-155-5p were found to be closely related with SHED odontogenic differentiation through whole-genome sequencing. The aim of the current study was to determine the role of miR-335-3p/miR-155-5p in IGFBP7-AS1-enhanced SHED differentiation and explore the potential mechanism of IGFBP7-AS1-mediated odontogenesis. METHODS Putative miR-335-3p/miR-155-5p binding sites within IGFBP7-AS1 were identified by bioinformatics analysis, and the binding of miR-335-3p/miR-155-5p to these sites was confirmed by dual-luciferase reporter gene assays. The effects of miR-335-3p/miR-155-5p in odontogenesis were detected by tissue nonspecific alkaline phosphatase staining, Alizarin red staining, quantitative real-time polymerase chain reaction (qRT-PCR) analyses, and western blot testing. The molecular mechanisms of miR-335-3p/miR-155-5p involved in IGFBP7-AS1-mediated odontogenesis were analysed by qRT-PCR and western blot testing. RESULTS Dual-luciferase reporter gene assays showed that miR-335-3p/miR-155-5p could directly bind to IGFBP7-AS1. MiR-335-3p and miR-155-5p both could down-regulate dentin sialophosphoprotein expression, and both miRNAs could inhibit IGFBP7-AS1-mediated SHED odontogenetic differentiation via suppression of the extracellular signal-regulated kinase (ERK) pathway. CONCLUSIONS Both miR-335-3p and miR-155-5p were negative regulators to IGFBP7-AS1-enhanced odontogenic differentiation of SHED through suppression of the ERK pathway.
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Affiliation(s)
- Ningxin Zhu
- Department of Pediatric Dentistry, Peking University School and Hospital of Stomatology & National Center of Stomatology & National Clinical Research Center for Oral Diseases
| | - Dan Wang
- Department of Pediatric Dentistry, Peking University School and Hospital of Stomatology & National Center of Stomatology & National Clinical Research Center for Oral Diseases
| | - Fei Xie
- Department of Pediatric Dentistry, Peking University School and Hospital of Stomatology & National Center of Stomatology & National Clinical Research Center for Oral Diseases
| | - Man Qin
- Department of Pediatric Dentistry, Peking University School and Hospital of Stomatology & National Center of Stomatology & National Clinical Research Center for Oral Diseases
| | - Yuanyuan Wang
- Department of Pediatric Dentistry, Peking University School and Hospital of Stomatology & National Center of Stomatology & National Clinical Research Center for Oral Diseases.
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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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Shi Q, Zheng M. Role of LINC01133 in Osteogenic Differentiation of Dental Pulp Stem Cells by Targeting miR-199b-5p. ORAL HEALTH & PREVENTIVE DENTISTRY 2022; 20:173-184. [PMID: 35481341 PMCID: PMC11641068 DOI: 10.3290/j.ohpd.b2960495] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Subscribe] [Scholar Register] [Received: 08/11/2021] [Accepted: 02/21/2022] [Indexed: 06/14/2023]
Abstract
PURPOSE Recently, increasing attention has been paid to the function of long non-coding RNAs (lncRNAs) in osteogenic differentiation (OD) of dental pulp stem cells (DPSCs). LINC01133 was reported to have a close relationship with tumorigenesis for multiple cancers, but no study has yet explored the role of LINC01133 in modulating OD of DPSCs. MATERIALS AND METHODS Alizarin red S (ARS) staining and alkaline phosphatase (ALP) staining were perfomed to assess the OD potential of DPSCs. Osteogenic markers including runt-related transcription factor 2 (RUNX2), osterix (OSX) and ALP expression levels in DPSCs were monitored by qRT-PCR and Western blot before and after cell transfection. Luciferase reporter gene assay detected the relationship between LINC01133 and miR-199b-5p. RESULTS The expression of LINC01133 was low, while miR-199b-5p was increasingly expressed during OD of DPSCs. Overexpression of LINC01133 in DPSCs resulted in decreased expression of RUNX2, OSX, ALP, DSPP and DMP1, whose expression was reversed in DPSCs after transfections of miR-199b-5p overexpression. Co-transfection of pcDNA3.1-LINC01133 and miR-199b-5p mimic led to elevated expression of RUNX2, OSX, ALP, DSPP and DMP1 compared with pcDNA3.1-LINC01133 transfection alone. LINC01133 served as a sponge of miR-199b-5p. AKT3 was verified as a downstream effector of miR-199b-5p in DPSCs. CONCLUSION LINC01133 inhibits the OD of DPSCs by upregulating AKT3 via sponging miR-199b-5p, which may act as a potential diagnostic biomarker for dentin regeneration in the dental pulp.
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Affiliation(s)
- Qiaorui Shi
- Physician, Department of Special Clinic, School and Hospital of Stomatology, Fujian Medical University, Fujian Stomatological Hospital, Fuzhou, Fujian, P.R. China. Idea, experimental design, performed the experiments, analysed the data, wrote the manuscript, read and approved the final version for publication
| | - Ming Zheng
- Chief Physician, Department of Oral Prosthetics, School and Hospital of Stomatology, Fujian Medical University, Fujian Stomatological Hospital, Fuzhou, Fujian, P.R. China; Fujian Key Laboratory of Oral Diseases, Laboratory of Oral Tissue Engineering, Fujian Medical University, Fuzhou, Fujian, P.R. China. Idea, experimental design, provided crucial materials, supervised the study, read and approved the final version of the manuscript for publication
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8
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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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Luo Y, Qiu W, Wu B, Fang F. An Overview of Mesenchymal Stem Cell-based Therapy Mediated by Noncoding RNAs in the Treatment of Neurodegenerative Diseases. Stem Cell Rev Rep 2022; 18:457-473. [PMID: 34347272 DOI: 10.1007/s12015-021-10206-x] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 06/11/2021] [Indexed: 12/11/2022]
Abstract
Mesenchymal stem cells (MSCs) have become a promising tool for neurorestorative therapy of neurodegenerative diseases (NDDs), which are mainly characterized by the progressive and irreversible loss of neuronal structure and function in the central or peripheral nervous system. Recently, studies have reported that genetic manipulation mediated by noncoding RNAs (ncRNAs) can increase survival and neural regeneration of transplanted MSCs, offering a new strategy for clinical translation. In this review, we summarize the potential role and regulatory mechanism of two major types of ncRNAs, including microRNAs (miRNAs) and long noncoding RNAs (lncRNAs), during the neurogenesis of MSCs with gene expression profile analyses. We also overview the realization of MSC-based therapy mediated by ncRNAs in the treatment of spinal cord injury, stroke, Alzheimer's disease and peripheral nerve injury. It is expected that ncRNAs will become promising therapeutic targets for NDD on stem cells, while the underlying mechanisms require further exploration.
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Affiliation(s)
- Yifei Luo
- Department of Stomatology, Nanfang Hospital, Southern Medical University, 1838 Guangzhou Avenue North, Guangzhou, 510515, People's Republic of China
| | - Wei Qiu
- Department of Stomatology, Nanfang Hospital, Southern Medical University, 1838 Guangzhou Avenue North, Guangzhou, 510515, People's Republic of China
| | - Buling Wu
- Department of Stomatology, Nanfang Hospital, Southern Medical University, 1838 Guangzhou Avenue North, Guangzhou, 510515, People's Republic of China
- Shenzhen Stomatology Hospital (Pingshan), Southern Medical University, 143 Dongzong Road, Pingshan District, Shenzhen, 518118, People's Republic of China
| | - Fuchun Fang
- Department of Stomatology, Nanfang Hospital, Southern Medical University, 1838 Guangzhou Avenue North, Guangzhou, 510515, People's Republic of China.
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De la Fuente-Hernandez MA, Sarabia-Sanchez MA, Melendez-Zajgla J, Maldonado-Lagunas V. Role of lncRNAs into Mesenchymal Stromal Cell Differentiation. Am J Physiol Cell Physiol 2022; 322:C421-C460. [PMID: 35080923 DOI: 10.1152/ajpcell.00364.2021] [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] [Indexed: 11/22/2022]
Abstract
Currently, findings support that 75% of the human genome is actively transcribed, but only 2% is translated into a protein, according to databases such as ENCODE (Encyclopedia of DNA Elements) [1]. The development of high-throughput sequencing technologies, computational methods for genome assembly and biological models have led to the realization of the importance of the previously unconsidered non-coding fraction of the genome. Along with this, noncoding RNAs have been shown to be epigenetic, transcriptional and post-transcriptional regulators in a large number of cellular processes [2]. Within the group of non-coding RNAs, lncRNAs represent a fascinating field of study, given the functional versatility in their mode of action on their molecular targets. In recent years, there has been an interest in learning about lncRNAs in MSC differentiation. The aim of this review is to address the signaling mechanisms where lncRNAs are involved, emphasizing their role in either stimulating or inhibiting the transition to differentiated cell. Specifically, the main types of MSC differentiation are discussed: myogenesis, osteogenesis, adipogenesis and chondrogenesis. The description of increasingly new lncRNAs reinforces their role as players in the well-studied field of MSC differentiation, allowing a step towards a better understanding of their biology and their potential application in the clinic.
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Affiliation(s)
- Marcela Angelica De la Fuente-Hernandez
- Facultad de Medicina, Posgrado en Ciencias Biológicas, Universidad Nacional Autónoma de México, Mexico City, Mexico.,Laboratorio de Epigenética, Instituto Nacional de Medicina Genómica, Mexico City, Mexico
| | - Miguel Angel Sarabia-Sanchez
- Facultad de Medicina, Posgrado en Ciencias Bioquímicas, Universidad Nacional Autónoma de México, Mexico City, Mexico
| | - Jorge Melendez-Zajgla
- Laboratorio de Genómica Funcional del Cáncer, Instituto Nacional de Medicina Genómica, Mexico City, Mexico
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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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12
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Liu Y, Gan L, Cui DX, Yu SH, Pan Y, Zheng LW, Wan M. Epigenetic regulation of dental pulp stem cells and its potential in regenerative endodontics. World J Stem Cells 2021; 13:1647-1666. [PMID: 34909116 PMCID: PMC8641018 DOI: 10.4252/wjsc.v13.i11.1647] [Citation(s) in RCA: 21] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/28/2021] [Revised: 06/07/2021] [Accepted: 11/03/2021] [Indexed: 02/06/2023] Open
Abstract
Regenerative endodontics (RE) therapy means physiologically replacing damaged pulp tissue and regaining functional dentin–pulp complex. Current clinical RE procedures recruit endogenous stem cells from the apical papilla, periodontal tissue, bone marrow and peripheral blood, with or without application of scaffolds and growth factors in the root canal space, resulting in cementum-like and bone-like tissue formation. Without the involvement of dental pulp stem cells (DPSCs), it is unlikely that functional pulp regeneration can be achieved, even though acceptable repair can be acquired. DPSCs, due to their specific odontogenic potential, high proliferation, neurovascular property, and easy accessibility, are considered as the most eligible cell source for dentin–pulp regeneration. The regenerative potential of DPSCs has been demonstrated by recent clinical progress. DPSC transplantation following pulpectomy has successfully reconstructed neurovascularized pulp that simulates the physiological structure of natural pulp. The self-renewal, proliferation, and odontogenic differentiation of DPSCs are under the control of a cascade of transcription factors. Over recent decades, epigenetic modulations implicating histone modifications, DNA methylation, and noncoding (nc)RNAs have manifested as a new layer of gene regulation. These modulations exhibit a profound effect on the cellular activities of DPSCs. In this review, we offer an overview about epigenetic regulation of the fate of DPSCs; in particular, on the proliferation, odontogenic differentiation, angiogenesis, and neurogenesis. We emphasize recent discoveries of epigenetic molecules that can alter DPSC status and promote pulp regeneration through manipulation over epigenetic profiles.
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Affiliation(s)
- Ying Liu
- State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Department of Pediatric Dentistry, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, Sichuan Province, China
| | - Lu Gan
- State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Department of Pediatric Dentistry, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, Sichuan Province, China
| | - Di-Xin Cui
- State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Department of Pediatric Dentistry, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, Sichuan Province, China
| | - Si-Han Yu
- State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Department of Pediatric Dentistry, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, Sichuan Province, China
| | - Yue Pan
- State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Department of Pediatric Dentistry, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, Sichuan Province, China
| | - Li-Wei Zheng
- State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Department of Pediatric Dentistry, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, Sichuan Province, China
| | - Mian Wan
- 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 610041, Sichuan Province, China
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13
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Overexpression of long noncoding RNA MCM3AP-AS1 promotes osteogenic differentiation of dental pulp stem cells via miR-143-3p/IGFBP5 axis. Hum Cell 2021; 35:150-162. [PMID: 34822133 DOI: 10.1007/s13577-021-00648-3] [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: 06/11/2021] [Accepted: 11/12/2021] [Indexed: 10/19/2022]
Abstract
MCM3AP-AS1 regulates the cartilage repair in osteoarthritis, but how it regulates osteogenic differentiation of dental pulp stem cells (DPSCs) remains to be determined. DPSCs were isolated and induced for osteogenic differentiation. MCM3AP-AS1 expression was increased along with the osteogenic differentiation of DPSCs, whose expression was positive correlated with those of OCN, alkaline phosphatase (ALP) and RUNX2. On contrary, miR-143-3p expression was decreased along with the osteogenic differentiation and was negatively correlated with those of OCN, ALP and RUNX2. Dual-luciferase reporter gene assay showed that miR-143-3p can be negatively regulated by MCM3AP-AS1 and can regulate IGFBP5. MCM3AP-AS1 overexpression increased the expression levels of osteogenesis-specific genes, ALP activity and mineralized nodules during DPSC osteogenic differentiation, while IGFBP5 knockdown or miR-143-3p overexpression counteracted the effect of MCM3AP-AS1 overexpression in DPSCs. Therefore, this study demonstrated the role of MCM3AP-AS1/miR-143-3p/IGFBP5 axis in regulating DPSC osteogenic differentiation.
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Xu J, Yin Y, Lin Y, Tian M, Liu T, Li X, Chen S. Long non-coding RNAs: Emerging roles in periodontitis. J Periodontal Res 2021; 56:848-862. [PMID: 34296758 DOI: 10.1111/jre.12910] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/04/2021] [Revised: 05/15/2021] [Accepted: 05/27/2021] [Indexed: 02/05/2023]
Abstract
Periodontitis is a major burden of public health, affecting 20%-50% of the global population. It is a complex inflammatory disease characterized by the destruction of supporting structures of the teeth, leading to tooth loss and the emergence or worsening of systematic diseases. Understanding the molecular mechanisms underlying the physiopathology of periodontitis is beneficial for targeted therapeutics. Long non-coding RNAs (lncRNAs), transcripts made up of more than 200 nucleotides, have emerged as novel regulators of many biological and pathological processes. Recently, an increasing number of dysregulated lncRNAs have been found to be implicated in periodontitis. In this review, an overview of lncRNAs, including their biogenesis, characteristics, function mechanisms and research approaches, is provided. And we summarize recent research reports on the emerging roles of lncRNAs in regulating proliferation, apoptosis, inflammatory responses, and osteogenesis of periodontal cells to elucidate lncRNAs related physiopathology of periodontitis. Furthermore, we have highlighted the underlying mechanisms of lncRNAs in periodontitis pathology by interacting with microRNAs. Finally, the potential clinical applications, current challenges, and prospects of lncRNAs as diagnostic and prognostic biomarkers and therapeutic targets for periodontitis disease are discussed.
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Affiliation(s)
- Jingchen Xu
- State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Department of Orthodontics, West China Hospital of Stomatology, Sichuan University, Chengdu, China
| | - Yuanyuan Yin
- State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Department of Orthodontics, West China Hospital of Stomatology, Sichuan University, Chengdu, China
| | - Yao Lin
- State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Department of Orthodontics, West China Hospital of Stomatology, Sichuan University, Chengdu, China
| | - Mi Tian
- State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Department of Orthodontics, West China Hospital of Stomatology, Sichuan University, Chengdu, China
| | - Ting Liu
- State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Department of Orthodontics, West China Hospital of Stomatology, Sichuan University, Chengdu, China
| | - Xinyi Li
- State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Department of Orthodontics, West China Hospital of Stomatology, Sichuan University, Chengdu, China
| | - Song Chen
- State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Department of Orthodontics, West China Hospital of Stomatology, Sichuan University, Chengdu, China
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15
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Wang J, Liu X, Wang Y, Xin B, Wang W. The role of long noncoding RNA THAP9-AS1 in the osteogenic differentiation of dental pulp stem cells via the miR-652-3p/VEGFA axis. Eur J Oral Sci 2021; 129:e12790. [PMID: 34288157 DOI: 10.1111/eos.12790] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/27/2020] [Revised: 03/15/2021] [Accepted: 03/25/2021] [Indexed: 12/18/2022]
Abstract
Dental pulp stem cells (DPSCs) are multipotent and may play crucial roles in dentin-pulp regeneration. Recent studies have revealed that long noncoding RNAs (lncRNAs) are implicated in the osteogenic differentiation of DPSCs. However, the specific role and potential mechanisms of the lncRNA trihydroxyacetophenone domain containing nine antisense RNA 1 (THAP9-AS1) during osteogenic differentiation of DPSCs remain unknown. In the present study, we determined that THAP9-AS1 expression was upregulated during osteogenic differentiation of DPSCs. Moreover, we investigated the biological functions of THAP9-AS1 during osteogenic differentiation of DPSCs by loss-of-function assays. THAP9-AS1 knockdown inhibited osteogenic differentiation of DPSCs by decreasing alkaline phosphatase activity, alkaline phosphatase-positive cell ratio, mineralizing matrix and mRNA, and protein levels of early osteogenic-markers. We also found that THAP9-AS1 interacted with miR-652-3p, whose downstream gene target is vascular endothelial growth factor A (VEGFA). In addition, rescue assays indicated that VEGFA rescued the effects of THAP9-AS1 knockdown during osteogenic differentiation of DPSCs. In summary, we verified that knockdown of THAP9-AS1 inhibits osteogenic differentiation of DPSCs via the miR-652-3p/VEGFA axis. Our findings may be helpful to extend research on the mechanisms underlying osteogenic differentiation of DPSCs.
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Affiliation(s)
- Jia Wang
- Department of Cariology and Endodontology, Qingdao Stomatological Hospital Affiliated to Qingdao University, Qingdao, Shandong, China
| | - Xueyu Liu
- Department of Cariology and Endodontology, Qingdao Stomatological Hospital Affiliated to Qingdao University, Qingdao, Shandong, China
| | - Yue Wang
- Department of Stomatology, Qingdao Eighth People's Hospital, Qingdao, Shandong, China
| | - Bingchang Xin
- Department of Cariology and Endodontology, Qingdao Stomatological Hospital Affiliated to Qingdao University, Qingdao, Shandong, China
| | - Wei Wang
- Department of Prosthodontics, Qingdao Stomatological Hospital Affiliated to Qingdao University, Qingdao, Shandong, China
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Yin JY, Luo XH, Feng WQ, Miao SH, Ning TT, Lei Q, Jiang T, Ma DD. Multidifferentiation potential of dental-derived stem cells. World J Stem Cells 2021; 13:342-365. [PMID: 34136070 PMCID: PMC8176842 DOI: 10.4252/wjsc.v13.i5.342] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/21/2020] [Revised: 03/10/2021] [Accepted: 04/05/2021] [Indexed: 02/06/2023] Open
Abstract
Tooth-related diseases and tooth loss are widespread and are a major public health issue. The loss of teeth can affect chewing, speech, appearance and even psychology. Therefore, the science of tooth regeneration has emerged, and attention has focused on tooth regeneration based on the principles of tooth development and stem cells combined with tissue engineering technology. As undifferentiated stem cells in normal tooth tissues, dental mesenchymal stem cells (DMSCs), which are a desirable source of autologous stem cells, play a significant role in tooth regeneration. Researchers hope to reconstruct the complete tooth tissues with normal functions and vascularization by utilizing the odontogenic differentiation potential of DMSCs. Moreover, DMSCs also have the ability to differentiate towards cells of other tissue types due to their multipotency. This review focuses on the multipotential capacity of DMSCs to differentiate into various tissues, such as bone, cartilage, tendon, vessels, neural tissues, muscle-like tissues, hepatic-like tissues, eye tissues and glands and the influence of various regulatory factors, such as non-coding RNAs, signaling pathways, inflammation, aging and exosomes, on the odontogenic/osteogenic differentiation of DMSCs in tooth regeneration. The application of DMSCs in regenerative medicine and tissue engineering will be improved if the differentiation characteristics of DMSCs can be fully utilized, and the factors that regulate their differentiation can be well controlled.
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Affiliation(s)
- Jing-Yao Yin
- Department of Stomatology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, Guangdong Province, China
| | - Xing-Hong Luo
- Department of Stomatology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, Guangdong Province, China
| | - Wei-Qing Feng
- Department of Stomatology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, Guangdong Province, China
| | - Sheng-Hong Miao
- Department of Stomatology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, Guangdong Province, China
| | - Ting-Ting Ning
- Department of Endodontics, Stomatological Hospital, Southern Medical University, Guangzhou 510280, Guangdong Province, China
| | - Qian Lei
- Department of Stomatology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, Guangdong Province, China
| | - Tao Jiang
- Department of Stomatology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, Guangdong Province, China
| | - Dan-Dan Ma
- Department of Endodontics, Stomatological Hospital, Southern Medical University, Guangzhou 510280, Guangdong Province, China
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Abstract
Osteoporosis is a common bone disease characterized by low bone mass and deterioration of bone microstructure, which predisposes to higher risks of bone fragility and bone fracture. Long non-coding RNAs (lncRNAs) are a class of RNAs with a length of > 200 nucleotides without protein-coding function, which control the expression of genes and affect multiple biological processes. Accumulating evidence suggests that lncRNAs are widely involved in the molecular mechanisms of osteoporosis. This review aims to summarize the function and underlying mechanism of lncRNAs involved in the development of osteoporosis, and how it contributes to osteoblast and osteoclast function. This knowledge will shed new light on the modulation and potential treatment of osteoporosis.
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Affiliation(s)
- Yinxi He
- Department of Orthopaedic Trauma, The Third Hospital of Shijiazhuang, Shijiazhuang, 050000, Hebei, People's Republic of China
| | - Yanxia Chen
- Department of Endocrinology, The Second Hospital of Hebei Medical University, 215 Hepingxi Road, Shijiazhuang, 050000, Hebei, People's Republic of China.
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18
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Epigenetic Regulation of Dental Pulp Stem Cell Fate. Stem Cells Int 2020; 2020:8876265. [PMID: 33149742 PMCID: PMC7603635 DOI: 10.1155/2020/8876265] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/23/2020] [Revised: 09/21/2020] [Accepted: 09/24/2020] [Indexed: 02/05/2023] Open
Abstract
Epigenetic regulation, mainly involving DNA methylation, histone modification, and noncoding RNAs, affects gene expression without modifying the primary DNA sequence and modulates cell fate. Mesenchymal stem cells derived from dental pulp, also called dental pulp stem cells (DPSCs), exhibit multipotent differentiation capacity and can promote various biological processes, including odontogenesis, osteogenesis, angiogenesis, myogenesis, and chondrogenesis. Over the past decades, increased attention has been attracted by the use of DPSCs in the field of regenerative medicine. According to a series of studies, epigenetic regulation is essential for DPSCs to differentiate into specialized cells. In this review, we summarize the mechanisms involved in the epigenetic regulation of the fate of DPSCs.
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Liu Z, Xu S, Dao J, Gan Z, Zeng X. Differential expression of lncRNA/miRNA/mRNA and their related functional networks during the osteogenic/odontogenic differentiation of dental pulp stem cells. J Cell Physiol 2019; 235:3350-3361. [PMID: 31549394 DOI: 10.1002/jcp.29223] [Citation(s) in RCA: 39] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/05/2019] [Accepted: 09/03/2019] [Indexed: 12/30/2022]
Abstract
Dentin-pulp regeneration requires dental pulp stem cells (DPSCs), but the role of long noncoding RNAs (lncRNAs) during this process remains unclear. Here, we cultured human DPSCs in osteogenic/odontogenic medium for 14 days and analyzed cells via RNA-sequencing. The data were validated by quantitative reverse transcription-polymerase chain reaction and lncRNA-microRNA (miRNA)-messenger RNA (mRNA) networks were constructed to reveal the potential competing endogenous RNA regulatory role of lncRNAs. Kyoto Encyclopedia of Genes and Genomes and Gene Ontology enrichment analysis were performed. One lncRNA, SNHG7, was identified and validated by genetic shRNA silencing. A total of 89 lncRNAs, 1,636 mRNAs, and 113 miRNAs were differentially expressed after differentiation. Bioinformatics identified an array of affected signaling pathways including phosphoinositide-3-kinase-protein kinase B, transforming growth factor-β, and Wnt. mRNAs were enriched in cell migration, cell differentiation, stem cell development, ossification, and skeletal development. One lncRNA, SNHG7, was indentified to inhibit the odonto/osteogenic differentiation of DPSCs when silenced. In summary, we reveal several lncRNAs that significantly change during DPSC differentiation, including SNHG7. This reveals new targets for dentin-pulp complex regeneration and tissue engineering.
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Affiliation(s)
- Zhongjun Liu
- Department of Endodontics, Stomatological Hospital, Southern Medical University, Guangzhou, China
| | - Shuaimei Xu
- Department of Endodontics, Stomatological Hospital, Southern Medical University, Guangzhou, China.,Department of Immunology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, China
| | - Junfeng Dao
- Department of Prosthodontics, Stomatological Hospital, Southern Medical University, Guangzhou, China
| | - Zekun Gan
- Department of Periodontology and Implantology, Stomatological Hospital, Southern Medical University, Guangzhou, China
| | - Xiongqun Zeng
- Department of Endodontics, Stomatological Hospital, Southern Medical University, Guangzhou, China
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20
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Liu Y, Liu C, Zhang A, Yin S, Wang T, Wang Y, Wang M, Liu Y, Ying Q, Sun J, Wei F, Liu D, Wang C, Ge S. Down-regulation of long non-coding RNA MEG3 suppresses osteogenic differentiation of periodontal ligament stem cells (PDLSCs) through miR-27a-3p/IGF1 axis in periodontitis. Aging (Albany NY) 2019; 11:5334-5350. [PMID: 31398715 PMCID: PMC6710065 DOI: 10.18632/aging.102105] [Citation(s) in RCA: 73] [Impact Index Per Article: 12.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/03/2019] [Accepted: 07/12/2019] [Indexed: 12/11/2022]
Abstract
Objective: This study aimed to investigate the roles of long noncoding RNA (lncRNA) maternally expressed gene 3 (MEG3) in osteogenic differentiation of periodontal ligament stem cells (PDLSCs) in periodontitis. Methods: Differentially expressed lncRNAs and mRNAs between periodontitis periodontal ligament tissues and healthy periodontal ligament tissues were selected out using R project. PDLSCs were identified using flow cytometry. Western blot was employed to detect pathway relative proteins. Besides, targeted relationships between lncRNA and miRNA, as well as miRNA and mRNA were verified by dual luciferase reporter gene assay. Osteogenic differentiation of PDLSCs was assessed by alkaline phosphatase (ALP) staining and Alizarin Red Staining (ARS). Markers for osteoblast (Runx2, Osterix, Osteocalcin, Colla1) were detected using western blot. Results: LncRNA MEG3 and IGF1 were both down-regulated, while miR-27a-3p was up-regulated in periodontitis samples compared with healthy samples. Overexpression of MEG3 promoted osteogenic differentiation by enhancing expression of IGF1 yet suppressing expression of miRNA-27a-3p. Meanwhile, the results of ALP and ARS staining indicated that up-regulation of lncRNA MEG3 or IGF1 promoted osteogenic differentiation in PDLSCs, which could be reversed with up-regulation of miRNA-27a-3p. Conclusion: Down-regulation of MEG3 suppressed osteogenic differentiation of PDLSCs through miR-27a-3p/IGF1 axis in periodontitis.
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Affiliation(s)
- Yi Liu
- Shandong Provincial Key Laboratory of Oral Tissue Regeneration, School of Stomatology, Shandong University, Jinan, Shandong 250012, China.,Department of Orthodontics, School of Stomatology, Shandong University, Jinan, Shandong 250012, China
| | - Chunpeng Liu
- Shandong Provincial Key Laboratory of Oral Tissue Regeneration, School of Stomatology, Shandong University, Jinan, Shandong 250012, China.,Department of Orthodontics, School of Stomatology, Shandong University, Jinan, Shandong 250012, China
| | - Ankui Zhang
- Shandong Provincial Key Laboratory of Oral Tissue Regeneration, School of Stomatology, Shandong University, Jinan, Shandong 250012, China.,Department of Orthodontics, School of Stomatology, Shandong University, Jinan, Shandong 250012, China
| | - Shichang Yin
- Shandong Provincial Key Laboratory of Oral Tissue Regeneration, School of Stomatology, Shandong University, Jinan, Shandong 250012, China.,Department of Orthodontics, School of Stomatology, Shandong University, Jinan, Shandong 250012, China
| | - Ting Wang
- Shandong Provincial Key Laboratory of Oral Tissue Regeneration, School of Stomatology, Shandong University, Jinan, Shandong 250012, China.,Department of General Dentistry, School of Stomatology, Shandong University, Jinan, Shandong 250012, China
| | - Yan Wang
- Shandong Provincial Key Laboratory of Oral Tissue Regeneration, School of Stomatology, Shandong University, Jinan, Shandong 250012, China
| | - Meiming Wang
- Shandong Provincial Key Laboratory of Oral Tissue Regeneration, School of Stomatology, Shandong University, Jinan, Shandong 250012, China
| | - Yixin Liu
- Shandong Provincial Key Laboratory of Oral Tissue Regeneration, School of Stomatology, Shandong University, Jinan, Shandong 250012, China
| | - Qiaohui Ying
- Shandong Provincial Key Laboratory of Oral Tissue Regeneration, School of Stomatology, Shandong University, Jinan, Shandong 250012, China
| | - Jinrui Sun
- Shandong Provincial Key Laboratory of Oral Tissue Regeneration, School of Stomatology, Shandong University, Jinan, Shandong 250012, China
| | - Fulan Wei
- Shandong Provincial Key Laboratory of Oral Tissue Regeneration, School of Stomatology, Shandong University, Jinan, Shandong 250012, China.,Department of Orthodontics, School of Stomatology, Shandong University, Jinan, Shandong 250012, China
| | - Dongxu Liu
- Shandong Provincial Key Laboratory of Oral Tissue Regeneration, School of Stomatology, Shandong University, Jinan, Shandong 250012, China.,Department of Orthodontics, School of Stomatology, Shandong University, Jinan, Shandong 250012, China
| | - Chunling Wang
- Shandong Provincial Key Laboratory of Oral Tissue Regeneration, School of Stomatology, Shandong University, Jinan, Shandong 250012, China.,Department of Orthodontics, School of Stomatology, Shandong University, Jinan, Shandong 250012, China
| | - Shaohua Ge
- Shandong Provincial Key Laboratory of Oral Tissue Regeneration, School of Stomatology, Shandong University, Jinan, Shandong 250012, China.,Department of Periodontology, School of Stomatology, Shandong University, Jinan, Shandong 250012, China
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21
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Li Z, Li N, Ge X, Pan Y, Lu J, Gobin R, Yan M, Yu J. Differential circular RNA expression profiling during osteogenic differentiation of stem cells from apical papilla. Epigenomics 2019; 11:1057-1073. [DOI: 10.2217/epi-2018-0184] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/27/2022] Open
Abstract
Aim: This study aimed to investigate the distinct expression pattern of circular RNAs (circRNAs) in stem cells from apical papilla (SCAPs) during osteogenesis. Materials & methods: Isolated SCAPs were cultured in growth medium or osteogenic medium, respectively. Total RNA was extracted and submitted to RNA-sequencing. Expression profiles of circRNAs and constructed circRNA–miRNA–mRNA networks were determined. Results: A total of 333 unregulated circRNAs and 317 downregulated circRNAs in osteogenic differentiation were detected. Bioinformatics analysis identified that several biological pathways may be associated with osteogenic differentiation of SCAPs. Moreover, ten circRNAs, 21 miRNAs and 19 mRNAs were selected to construct competing endogenous RNA networks. Conclusion: This study revealed that expression profiles of circRNAs were significantly altered and specific circRNAs might function as competing endogenous RNAs in SCAPs during osteogenic differentiation.
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Affiliation(s)
- Zehan Li
- Key Laboratory of Oral Diseases of Jiangsu Province & Stomatological Institute of Nanjing Medical University, 140 Hanzhong Road, Nanjing, Jiangsu 210029, PR China
- Endodontic Department, School of Stomatology, Nanjing Medical University, 136 Hanzhong Road, Nanjing, Jiangsu 210029, PR China
| | - Na Li
- Key Laboratory of Oral Diseases of Jiangsu Province & Stomatological Institute of Nanjing Medical University, 140 Hanzhong Road, Nanjing, Jiangsu 210029, PR China
- Endodontic Department, School of Stomatology, Nanjing Medical University, 136 Hanzhong Road, Nanjing, Jiangsu 210029, PR China
| | - Xingyun Ge
- Key Laboratory of Oral Diseases of Jiangsu Province & Stomatological Institute of Nanjing Medical University, 140 Hanzhong Road, Nanjing, Jiangsu 210029, PR China
- Endodontic Department, School of Stomatology, Nanjing Medical University, 136 Hanzhong Road, Nanjing, Jiangsu 210029, PR China
| | - Yin Pan
- Key Laboratory of Oral Diseases of Jiangsu Province & Stomatological Institute of Nanjing Medical University, 140 Hanzhong Road, Nanjing, Jiangsu 210029, PR China
- Endodontic Department, School of Stomatology, Nanjing Medical University, 136 Hanzhong Road, Nanjing, Jiangsu 210029, PR China
| | - Jiamin Lu
- Key Laboratory of Oral Diseases of Jiangsu Province & Stomatological Institute of Nanjing Medical University, 140 Hanzhong Road, Nanjing, Jiangsu 210029, PR China
- Endodontic Department, School of Stomatology, Nanjing Medical University, 136 Hanzhong Road, Nanjing, Jiangsu 210029, PR China
| | - Romila Gobin
- Key Laboratory of Oral Diseases of Jiangsu Province & Stomatological Institute of Nanjing Medical University, 140 Hanzhong Road, Nanjing, Jiangsu 210029, PR China
| | - Ming Yan
- Key Laboratory of Oral Diseases of Jiangsu Province & Stomatological Institute of Nanjing Medical University, 140 Hanzhong Road, Nanjing, Jiangsu 210029, PR China
- Endodontic Department, School of Stomatology, Nanjing Medical University, 136 Hanzhong Road, Nanjing, Jiangsu 210029, PR China
| | - Jinhua Yu
- Key Laboratory of Oral Diseases of Jiangsu Province & Stomatological Institute of Nanjing Medical University, 140 Hanzhong Road, Nanjing, Jiangsu 210029, PR China
- Endodontic Department, School of Stomatology, Nanjing Medical University, 136 Hanzhong Road, Nanjing, Jiangsu 210029, PR China
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Li J, Yang Y, Fan J, Xu H, Fan L, Li H, Zhao RC. Long noncoding RNA ANCR inhibits the differentiation of mesenchymal stem cells toward definitive endoderm by facilitating the association of PTBP1 with ID2. Cell Death Dis 2019; 10:492. [PMID: 31235689 PMCID: PMC6591386 DOI: 10.1038/s41419-019-1738-3] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/10/2019] [Revised: 05/17/2019] [Accepted: 06/10/2019] [Indexed: 12/28/2022]
Abstract
The generation of definitive endoderm (DE) cells in sufficient numbers is a prerequisite for cell-replacement therapy for liver and pancreatic diseases. Previously, we reported that human adipose-derived mesenchymal stem cells (hAMSCs) can be induced to DE lineages and subsequent functional cells. Clarifying the regulatory mechanisms underlying the fate conversion from hAMSCs to DE is helpful for developing new strategies to improve the differentiation efficiency from hAMSCs to DE organs. Long noncoding RNAs (lncRNAs) have been shown to play pivotal roles in developmental processes, including cell fate determination and differentiation. In this study, we profiled the expression changes of lncRNAs and found that antidifferentiation noncoding RNA (ANCR) was downregulated during the differentiation of both hAMSCs and embryonic stem cells (ESCs) to DE cells. ANCR knockdown resulted in the elevated expression of DE markers in hAMSCs, but not in ESCs. ANCR overexpression reduced the efficiency of hAMSCs to differentiate into DE cells. Inhibitor of DNA binding 2 (ID2) was notably downregulated after ANCR knockdown. ID2 knockdown enhanced DE differentiation, whereas overexpression of ID2 impaired this process in hAMSCs. ANCR interacts with RNA-binding polypyrimidine tract-binding protein 1 (PTBP1) to facilitate its association with ID2 mRNA, leading to increased ID2 mRNA stability. Thus, the ANCR/PTBP1/ID2 network restricts the differentiation of hAMSCs toward DE. Our work highlights the inherent discrepancies between hAMSCs and ESCs. Defining hAMSC-specific signaling pathways might be important for designing optimal differentiation protocols for directing hAMSCs toward DE.
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Affiliation(s)
- Jing Li
- Institute of Basic Medical Sciences Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, Peking Union Medical College Hospital, Beijing Key Laboratory of New Drug Development and Clinical Trial of Stem Cell Therapy (BZ0381), 100005, Beijing, China
| | - Yanlei Yang
- Institute of Basic Medical Sciences Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, Peking Union Medical College Hospital, Beijing Key Laboratory of New Drug Development and Clinical Trial of Stem Cell Therapy (BZ0381), 100005, Beijing, China
| | - Junfen Fan
- Institute of Basic Medical Sciences Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, Peking Union Medical College Hospital, Beijing Key Laboratory of New Drug Development and Clinical Trial of Stem Cell Therapy (BZ0381), 100005, Beijing, China
| | - Haoying Xu
- Institute of Basic Medical Sciences Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, Peking Union Medical College Hospital, Beijing Key Laboratory of New Drug Development and Clinical Trial of Stem Cell Therapy (BZ0381), 100005, Beijing, China
| | - Linyuan Fan
- Institute of Basic Medical Sciences Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, Peking Union Medical College Hospital, Beijing Key Laboratory of New Drug Development and Clinical Trial of Stem Cell Therapy (BZ0381), 100005, Beijing, China
| | - Hongling Li
- Institute of Basic Medical Sciences Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, Peking Union Medical College Hospital, Beijing Key Laboratory of New Drug Development and Clinical Trial of Stem Cell Therapy (BZ0381), 100005, Beijing, China.
| | - Robert Chunhua Zhao
- Institute of Basic Medical Sciences Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, Peking Union Medical College Hospital, Beijing Key Laboratory of New Drug Development and Clinical Trial of Stem Cell Therapy (BZ0381), 100005, Beijing, China.
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23
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Cai B, Wang X, Liu H, Ma S, Zhang K, Zhang Y, Li Q, Wang J, Yao M, Guan F, Yin G. Up-regulated lncRNA5322 elevates MAPK1 to enhance proliferation of hair follicle stem cells as a ceRNA of microRNA-19b-3p. Cell Cycle 2019; 18:1588-1600. [PMID: 31203719 DOI: 10.1080/15384101.2019.1624111] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/20/2023] Open
Abstract
Hair follicle stem cells (HFSCs), located in the bulge region of the follicle, maintain hair follicle growth and cycling. Long non-coding RNAs (lncRNAs), non-protein coding transcripts, are widely known to play critical roles in differentiation and proliferation of stem cells. Therefore, the current study aimed to explore the regulatory roles of lncRNA5322 in HFSCs proliferation and the underlying regulatory mechanisms. Initially, the expression patterns of lncRNA5322 and microRNA-19b-3p (miR-19b-3p) in HFSCs were detected. Subsequently, gain-and loss-of-functions analyses were conducted to explore the roles of lncRNA5322, miR-19b-3p and mitogen-activated protein kinase 1 (MAPK1) in cell proliferation, colony formation and apoptosis of HFSCs, with the expression of cyclin-dependent kinase (CDK)1 and CDK2 examined. Also, the interaction relationships among lncRNA5322, miR-19b-3p and MAPK1 were explored. Furthermore, a mouse model was established to detect the roles of lncRNA5322, miR-19b-3p, and MAPK1 in wound contraction and epidermal regeneration. Over-expressed lncRNA5322 was found to promote proliferation, colony formation ability but inhibit apoptosis of HFSCs, in addition to up-regulation of the expression of CDK1 and CDK2. LncRNA5322 was found to act as a ceRNA of miR-19b-3p which directly targeted MAPK1. Furthermore, up-regulation of lncRNA5322 enhanced wound contraction and epidermal regeneration in vivo by increasing the expression of MAPK1 through functioning as a ceRNA of miR-19b-3p. In summary, the results in this study suggested that lncRNA5322 serves as a ceRNA of miR-19b-3p to elevate the expression of MAPK1, ultimately promoting HFSCs proliferation, wound contraction and epidermal regeneration of mouse model.
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Affiliation(s)
- Bingjie Cai
- a The First Affiliated Hospital of Zhengzhou University , Zhengzhou , P.R. China
| | - Xinxin Wang
- a The First Affiliated Hospital of Zhengzhou University , Zhengzhou , P.R. China
| | - Hongtao Liu
- b School of Life Sciences , Zhengzhou University , Zhengzhou , P.R. China
| | - Shanshan Ma
- b School of Life Sciences , Zhengzhou University , Zhengzhou , P.R. China
| | - Kun Zhang
- b School of Life Sciences , Zhengzhou University , Zhengzhou , P.R. China
| | - Yanting Zhang
- b School of Life Sciences , Zhengzhou University , Zhengzhou , P.R. China
| | - Qinghua Li
- b School of Life Sciences , Zhengzhou University , Zhengzhou , P.R. China
| | - Junmin Wang
- c College of Basic Medical Sciences , Zhengzhou University , Zhengzhou , P.R. China
| | - Minghao Yao
- b School of Life Sciences , Zhengzhou University , Zhengzhou , P.R. China
| | - Fangxia Guan
- b School of Life Sciences , Zhengzhou University , Zhengzhou , P.R. China
| | - Guangwen Yin
- a The First Affiliated Hospital of Zhengzhou University , Zhengzhou , P.R. China
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24
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Wu L, Deng L, Hong H, Peng C, Zhang X, Chen Z, Ling J. Comparison of long non‑coding RNA expression profiles in human dental follicle cells and human periodontal ligament cells. Mol Med Rep 2019; 20:939-950. [PMID: 31173189 PMCID: PMC6625187 DOI: 10.3892/mmr.2019.10308] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/09/2018] [Accepted: 02/28/2019] [Indexed: 12/22/2022] Open
Abstract
The dental follicle develops into the periodontal ligament, cementum and alveolar bone. Human dental follicle cells (hDFCs) are the precursor cells of periodontal development. Long non-coding RNAs (lncRNAs) have been revealed to be crucial factors that regulate a variety of biological processes; however, whether lncRNAs serve a role in human periodontal development remains unknown. Therefore, the present study used microarrays to detect the differentially expressed lncRNAs and mRNAs between hDFCs and human periodontal ligament cells (hPDLCs). A total of 845 lncRNAs and 1,012 mRNAs were identified to be differentially expressed in hDFCs and hPDLCs (fold change >2.0 or <-2.0; P<0.05). Microarray data were validated by reverse transcription-quantitative polymerase chain reaction. Bioinformatics analyses, including gene ontology, pathway analysis and coding-non-coding gene co-expression network analysis, were performed to determine the functions of the differentially expressed lncRNAs and mRNAs. Bioinformatics analysis identified that a number of pathways may be associated with periodontal development, including the p53 and calcium signaling pathways. This analysis also revealed a number of lncRNAs, including NR_033932, T152410, ENST00000512129, ENST00000540293, uc021sxs.1 and ENST00000609146, which may serve important roles in the biological process of hDFCs. In addition, the lncRNA termed maternally expressed 3 (MEG3) was identified to be differentially expressed in hDFCs by reverse transcription-quantitative polymerase chain reaction. The knockdown of MEG3 was associated with a reduction of pluripotency makers in hDFCs. In conclusion, for the first time, to the best of our knowledge, the current study determined the different expression profiles of lncRNAs and mRNAs between hDFCs and hPDLCs. The observations made may provide a solid foundation for further research into the molecular mechanisms of lncRNAs in human periodontal development.
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Affiliation(s)
- Liping Wu
- Department of Orthodontics, Guanghua School of Stomatology, Guangdong Provincial Key Laboratory of Stomatology, Sun Yat‑Sen University, Guangzhou, Guangdong 510055, P.R. China
| | - Lidi Deng
- Department of Orthodontics, Guanghua School of Stomatology, Guangdong Provincial Key Laboratory of Stomatology, Sun Yat‑Sen University, Guangzhou, Guangdong 510055, P.R. China
| | - Hong Hong
- Zhujiang New Town Dental Clinic, Guanghua School of Stomatology, Guangdong Provincial Key Laboratory of Stomatology, Sun Yat‑Sen University, Guangzhou, Guangdong 510055, P.R. China
| | - Caixia Peng
- Department of Orthodontics, Guanghua School of Stomatology, Guangdong Provincial Key Laboratory of Stomatology, Sun Yat‑Sen University, Guangzhou, Guangdong 510055, P.R. China
| | - Xueqin Zhang
- Department of Orthodontics, Guanghua School of Stomatology, Guangdong Provincial Key Laboratory of Stomatology, Sun Yat‑Sen University, Guangzhou, Guangdong 510055, P.R. China
| | - Zhengyuan Chen
- Department of Orthodontics, Guanghua School of Stomatology, Guangdong Provincial Key Laboratory of Stomatology, Sun Yat‑Sen University, Guangzhou, Guangdong 510055, P.R. China
| | - Junqi Ling
- Department of Endodontics, Guanghua School of Stomatology, Guangdong Provincial Key Laboratory of Stomatology, Sun Yat‑Sen University, Guangzhou, Guangdong 510055, P.R. China
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25
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Zhang Y, Tao Y, Liao Q. Long noncoding RNA: a crosslink in biological regulatory network. Brief Bioinform 2019; 19:930-945. [PMID: 28449042 DOI: 10.1093/bib/bbx042] [Citation(s) in RCA: 92] [Impact Index Per Article: 15.3] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/04/2017] [Indexed: 01/17/2023] Open
Abstract
Long noncoding RNAs (lncRNAs) had been defined as a novel class of functional RNAs longer than 200 nucleotides around a decade ago. It is widely acknowledged that lncRNAs play a significant role in regulation of gene expression, but the biological and molecular mechanisms are diverse and complex, and remain to be determined. Especially, the regulatory network of lncRNAs associated with other biological molecules is still a controversial matter, thus becoming a new frontier of the studies on transcriptome. Recent advance in high-throughput sequencing technologies and bioinformatics approaches may be an accelerator to lift the mysterious veil. In this review, we will outline well-known associations between lncRNAs and other biological molecules, demonstrate the diverse bioinformatics approaches applied in prediction and analysis of lncRNA interaction and perform a case study for lncRNA linc00460 to concretely decipher the lncRNA regulatory network.
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Affiliation(s)
- Yuwei Zhang
- Department of Preventative Medicine, Zhejiang Provincial Key Laboratory of Pathological and Physiological Technology, Medicine School of Ningbo University, Ningbo, Zhejiang, China
| | - Yang Tao
- Department of Preventative Medicine, Zhejiang Provincial Key Laboratory of Pathological and Physiological Technology, Medicine School of Ningbo University, Ningbo, Zhejiang, China
| | - Qi Liao
- Department of Preventative Medicine, Zhejiang Provincial Key Laboratory of Pathological and Physiological Technology, Medicine School of Ningbo University, Ningbo, Zhejiang, China
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26
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Silva AM, Moura SR, Teixeira JH, Barbosa MA, Santos SG, Almeida MI. Long noncoding RNAs: a missing link in osteoporosis. Bone Res 2019; 7:10. [PMID: 30937214 PMCID: PMC6437190 DOI: 10.1038/s41413-019-0048-9] [Citation(s) in RCA: 75] [Impact Index Per Article: 12.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/22/2018] [Revised: 02/19/2019] [Accepted: 02/25/2019] [Indexed: 02/07/2023] Open
Abstract
Osteoporosis is a systemic disease that results in loss of bone density and increased fracture risk, particularly in the vertebrae and the hip. This condition and associated morbidity and mortality increase with population ageing. Long noncoding (lnc) RNAs are transcripts longer than 200 nucleotides that are not translated into proteins, but play important regulatory roles in transcriptional and post-transcriptional regulation. Their contribution to disease onset and development is increasingly recognized. Herein, we present an integrative revision on the studies that implicate lncRNAs in osteoporosis and that support their potential use as therapeutic tools. Firstly, current evidence on lncRNAs involvement in cellular and molecular mechanisms linked to osteoporosis and its major complication, fragility fractures, is reviewed. We analyze evidence of their roles in osteogenesis, osteoclastogenesis, and bone fracture healing events from human and animal model studies. Secondly, the potential of lncRNAs alterations at genetic and transcriptomic level are discussed as osteoporosis risk factors and as new circulating biomarkers for diagnosis. Finally, we conclude debating the possibilities, persisting difficulties, and future prospects of using lncRNAs in the treatment of osteoporosis.
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Affiliation(s)
- Andreia Machado Silva
- i3S—Instituto de Investigação e Inovação em Saúde, University of Porto, Porto, Portugal
- INEB—Instituto de Engenharia Biomédica, University of Porto, Porto, Portugal
| | - Sara Reis Moura
- i3S—Instituto de Investigação e Inovação em Saúde, University of Porto, Porto, Portugal
- INEB—Instituto de Engenharia Biomédica, University of Porto, Porto, Portugal
| | - José Henrique Teixeira
- i3S—Instituto de Investigação e Inovação em Saúde, University of Porto, Porto, Portugal
- INEB—Instituto de Engenharia Biomédica, University of Porto, Porto, Portugal
- ICBAS—Instituto de Ciências Biomédicas Abel Salazar, University of Porto, Porto, Portugal
| | - Mário Adolfo Barbosa
- i3S—Instituto de Investigação e Inovação em Saúde, University of Porto, Porto, Portugal
- INEB—Instituto de Engenharia Biomédica, University of Porto, Porto, Portugal
- ICBAS—Instituto de Ciências Biomédicas Abel Salazar, University of Porto, Porto, Portugal
| | - Susana Gomes Santos
- i3S—Instituto de Investigação e Inovação em Saúde, University of Porto, Porto, Portugal
- INEB—Instituto de Engenharia Biomédica, University of Porto, Porto, Portugal
- ICBAS—Instituto de Ciências Biomédicas Abel Salazar, University of Porto, Porto, Portugal
| | - Maria Inês Almeida
- i3S—Instituto de Investigação e Inovação em Saúde, University of Porto, Porto, Portugal
- INEB—Instituto de Engenharia Biomédica, University of Porto, Porto, Portugal
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27
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Abstract
Long non-coding RNAs (lncRNAs) are transcripts longer than 200 nucleotides with limited coding potential, which have emerged as novel regulators in many biological and pathological processes, including growth, development, and oncogenesis. Accumulating evidence suggests that lncRNAs have a special role in the osteogenic differentiation of various types of cell, including stem cells from different sources such as embryo, bone marrow, adipose tissue and periodontal ligaments, and induced pluripotent stem cells. Involved in complex mechanisms, lncRNAs regulate osteogenic markers and key regulators and pathways in osteogenic differentiation. In this review, we provide insights into the functions and molecular mechanisms of lncRNAs in osteogenesis and highlight their emerging roles and clinical value in regenerative medicine and osteogenesis-related diseases. Cite this article: J. Zhang, X. Hao, M. Yin, T. Xu, F. Guo. Long non-coding RNA in osteogenesis: A new world to be explored. Bone Joint Res 2019;8:73–80. DOI: 10.1302/2046-3758.82.BJR-2018-0074.R1.
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Affiliation(s)
- J Zhang
- Department of Orthopedics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China; Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China; Department of Biochemistery and Biophysics, Lineberger Comprehensive Cancer Center, University of North Carolina, North Carolina, USA
| | - X Hao
- Department of Rehabilitation, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - M Yin
- Department of Obstetrics and Gynecology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - T Xu
- Department of Rehabilitation, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - F Guo
- Department of Orthopedics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
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28
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Yang Q, Jia L, Li X, Guo R, Huang Y, Zheng Y, Li W. Long Noncoding RNAs: New Players in the Osteogenic Differentiation of Bone Marrow- and Adipose-Derived Mesenchymal Stem Cells. Stem Cell Rev Rep 2018; 14:297-308. [PMID: 29464508 DOI: 10.1007/s12015-018-9801-5] [Citation(s) in RCA: 47] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/26/2022]
Abstract
Mesenchymal stem cells (MSCs) are an important population of multipotent stem cells that differentiate into multiple lineages and display great potential in bone regeneration and repair. Although the role of protein-coding genes in the osteogenic differentiation of MSCs has been extensively studied, the functions of noncoding RNAs in the osteogenic differentiation of MSCs are unclear. The recent application of next-generation sequencing to MSC transcriptomes has revealed that long noncoding RNAs (lncRNAs) are associated with the osteogenic differentiation of MSCs. LncRNAs are a class of non-coding transcripts of more than 200 nucleotides in length. Noncoding RNAs are thought to play a key role in osteoblast differentiation through various regulatory mechanisms including chromatin modification, transcription factor binding, competent endogenous mechanism, and other post-transcriptional mechanisms. Here, we review the roles of lncRNAs in the osteogenic differentiation of bone marrow- and adipose-derived stem cells and provide a theoretical foundation for future research.
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Affiliation(s)
- Qiaolin Yang
- Department of Orthodontics, Peking University School and Hospital of Stomatology, 22 Zhongguancun Avenue South, Haidian District, Beijing, 100081, People's Republic of China
| | - Lingfei Jia
- Central Laboratory, Peking University School and Hospital of Stomatology, Beijing, 100081, People's Republic of China
- Department of Oral and Maxillofacial Surgery, Peking University School and Hospital of Stomatology, Beijing, 100081, People's Republic of China
| | - Xiaobei Li
- Department of Orthodontics, Peking University School and Hospital of Stomatology, 22 Zhongguancun Avenue South, Haidian District, Beijing, 100081, People's Republic of China
| | - Runzhi Guo
- Department of Orthodontics, Peking University School and Hospital of Stomatology, 22 Zhongguancun Avenue South, Haidian District, Beijing, 100081, People's Republic of China
| | - Yiping Huang
- Department of Orthodontics, Peking University School and Hospital of Stomatology, 22 Zhongguancun Avenue South, Haidian District, Beijing, 100081, People's Republic of China
| | - Yunfei Zheng
- Department of Orthodontics, Peking University School and Hospital of Stomatology, 22 Zhongguancun Avenue South, Haidian District, Beijing, 100081, People's Republic of China.
| | - Weiran Li
- Department of Orthodontics, Peking University School and Hospital of Stomatology, 22 Zhongguancun Avenue South, Haidian District, Beijing, 100081, People's Republic of China.
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Liu Y, Zeng X, Miao J, Liu C, Wei F, Liu D, Zheng Z, Ting K, Wang C, Guo J. Upregulation of long noncoding RNA MEG3 inhibits the osteogenic differentiation of periodontal ligament cells. J Cell Physiol 2018; 234:4617-4626. [PMID: 30256394 DOI: 10.1002/jcp.27248] [Citation(s) in RCA: 26] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/26/2018] [Accepted: 07/24/2018] [Indexed: 12/22/2022]
Abstract
OBJECTIVE This study aims to discuss long noncoding RNA (lncRNA) maternally expressed gene 3 (MEG3) function of regulating osteogenesis in human periodontal ligament cells (hPDLCs). METHODS First, use of a mineralizing solution induced osteogenic differentiation of hPDLCs to establish a differentiated cell model. Through microarray analysis, we selected a lncRNA MEG3 with marked changes between differentiated and undifferentiated cells. The quantitative polymerase chain reaction was used to detect the MEG3 content and an enzyme-linked immunosorbent assay was used to detect changes in related proteins. Cell viability was determined by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and apoptosis was measured by flow cytometry. Alizarin red staining was also used to evaluate cells' osteogenic level. Finally, RNA-binding protein immunoprecipitation assays were conducted to further clarify the endogenous relationship between MEG3 and bone morphogenetic protein 2 ( BMP2) in hPDLCs. RESULTS MEG3 was downregulated in osteogenic differentiation hPDLCs induced by mineralizing solution. Overexpression of MEG3 inhibited cell viability and increased cell apoptosis. MEG3 overexpression can reverse osteogenic differentiation induced by mineralizing solution. MEG3 can suppress BMP2 through interaction with heterogeneous nuclear ribonucleoprotein I. CONCLUSION Upregulation of MEG3 inhibits the osteogenic differentiation of periodontal ligament cells by downregulating BMP2 expression.
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Affiliation(s)
- Yi Liu
- Shandong Provincial Key Laboratory of Oral Tissue Regeneration, School of Stomatology, Shandong University, Jinan, China.,Department of Orthodontics, School of Stomatology, Shandong University, Jinan, China
| | - Xuemin Zeng
- Shandong Provincial Key Laboratory of Oral Tissue Regeneration, School of Stomatology, Shandong University, Jinan, China.,Department of Orthodontics, School of Stomatology, Shandong University, Jinan, China
| | - Jie Miao
- Department of Stomatology, The Fifth People's Hospital of Ji'nan, Jinan, China
| | - Chunpeng Liu
- Shandong Provincial Key Laboratory of Oral Tissue Regeneration, School of Stomatology, Shandong University, Jinan, China.,Department of Orthodontics, School of Stomatology, Shandong University, Jinan, China
| | - Fulan Wei
- Shandong Provincial Key Laboratory of Oral Tissue Regeneration, School of Stomatology, Shandong University, Jinan, China.,Department of Orthodontics, School of Stomatology, Shandong University, Jinan, China
| | - Dongxu Liu
- Shandong Provincial Key Laboratory of Oral Tissue Regeneration, School of Stomatology, Shandong University, Jinan, China.,Department of Orthodontics, School of Stomatology, Shandong University, Jinan, China
| | - Zhong Zheng
- Section of Orthodontics, Division of Growth and Development, School of Dentistry, University of California, Los Angeles, California.,UCLA Division of Plastic and Reconstructive Surgery, Department of Orthopaedic Surgery, The Orthopaedic Hospital Research Center, University of California, Los Angeles, California
| | - Kang Ting
- Section of Orthodontics, Division of Growth and Development, School of Dentistry, University of California, Los Angeles, California.,UCLA Division of Plastic and Reconstructive Surgery, Department of Orthopaedic Surgery, The Orthopaedic Hospital Research Center, University of California, Los Angeles, California
| | - Chunling Wang
- Shandong Provincial Key Laboratory of Oral Tissue Regeneration, School of Stomatology, Shandong University, Jinan, China.,Department of Orthodontics, School of Stomatology, Shandong University, Jinan, China
| | - Jie Guo
- Shandong Provincial Key Laboratory of Oral Tissue Regeneration, School of Stomatology, Shandong University, Jinan, China.,Department of Orthodontics, School of Stomatology, Shandong University, Jinan, China
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30
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Huang X, Chen K. Differential Expression of Long Noncoding RNAs in Normal and Inflamed Human Dental Pulp. J Endod 2017; 44:62-72. [PMID: 29079059 DOI: 10.1016/j.joen.2017.08.022] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/15/2016] [Revised: 08/08/2017] [Accepted: 08/15/2017] [Indexed: 12/20/2022]
Abstract
INTRODUCTION Dental pulp inflammation is an excellent model for the interaction between tissue inflammation and regenerative processes. It is worthwhile to better understand molecular signaling of repair and regeneration in inflammatory processes. Emerging evidence suggests that long noncoding RNA (lncRNA) participates in immune system inflammatory processes. Here we investigate the expression of lncRNAs in pulpitis, the inflammation of dental pulp tissue, and identify lncRNAs that possibly participate in inflammation responses and odontogenesis. METHODS Integrated comparative lncRNA microarray was used to examine lncRNA and mRNA expression between inflamed and normal human pulp tissue. The differential expression of lncRNAs and mRNAs was then validated by quantitative real-time polymerase chain reaction. A bioinformatics analysis was performed to predict the function of differentially expressed lncRNAs and mRNAs. RESULTS Our data indicated 752 lncRNAs were significantly differentially expressed (fold change > 2.0; P < .05) in inflamed pulp tissues compared with normal pulp tissues, including 338 upregulated and 414 downregulated lncRNAs. Among the 646 differentially expressed mRNAs (fold change > 2.0; P < .05), 460 were upregulated, and 186 were downregulated. The differentially downregulated genes are enriched for gene ontology terms related to odontogenesis and cell development in biological processes, whereas the differentially upregulated genes are related to immune and inflammation processes. CONCLUSIONS LncRNAs are differentially expressed in inflamed human pulp tissue compared with normal pulp tissue, indicating that lncRNAs may play key roles in pulpitis pathogenesis and development.
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Affiliation(s)
- Xin Huang
- Department of Stomatology, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, China
| | - Ke Chen
- Department of Stomatology, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, China.
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