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Yin Y, Shuai F, Liu X, Zhao Y, Han X, Zhao H. Biomaterials and therapeutic strategies designed for tooth extraction socket healing. Biomaterials 2025; 316:122975. [PMID: 39626339 DOI: 10.1016/j.biomaterials.2024.122975] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/23/2024] [Revised: 11/16/2024] [Accepted: 11/28/2024] [Indexed: 12/31/2024]
Abstract
Tooth extraction is the most commonly performed oral surgical procedure, with a wide range of clinical indications. The oral cavity is a complex microenvironment, influenced by oral movements, salivary flow, and bacterial biofilms. These factors can contribute to delayed socket healing and the onset of post-extraction complications, which can burden patients' esthetic and functional rehabilitation. Achieving effective extraction socket healing requires a multidisciplinary approach. Recent advancements in materials science and bioengineering have paved the way for developing novel strategies. This review outlines the fundamental healing processes and cellular-molecular interactions involved in the healing of extraction sockets. It then delves into the current landscape of biomaterials for socket healing, highlighting emerging strategies and potential targets that could transform the treatment paradigm. Building upon this foundation, this review also presents future directions and identifies challenges associated with the clinical application of biomaterials for extraction socket healing.
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Affiliation(s)
- Yijia Yin
- State Key Laboratory of Oral Diseases, National Center for Stomatology, National Clinical Research Center for Oral Diseases, Department of Orthodontics, Department of Oral and Maxillofacial Surgery, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan, 610041, PR China
| | - Fangyuan Shuai
- State Key Laboratory of Oral Diseases, National Center for Stomatology, National Clinical Research Center for Oral Diseases, Department of Orthodontics, Department of Oral and Maxillofacial Surgery, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan, 610041, PR China
| | - Xian Liu
- State Key Laboratory of Oral Diseases, National Center for Stomatology, National Clinical Research Center for Oral Diseases, Department of Orthodontics, Department of Oral and Maxillofacial Surgery, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan, 610041, PR China
| | - Yuxi Zhao
- State Key Laboratory of Oral Diseases, National Center for Stomatology, National Clinical Research Center for Oral Diseases, Department of Orthodontics, Department of Oral and Maxillofacial Surgery, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan, 610041, PR China
| | - Xianglong Han
- State Key Laboratory of Oral Diseases, National Center for Stomatology, National Clinical Research Center for Oral Diseases, Department of Orthodontics, Department of Oral and Maxillofacial Surgery, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan, 610041, PR China.
| | - Hang Zhao
- State Key Laboratory of Oral Diseases, National Center for Stomatology, National Clinical Research Center for Oral Diseases, Department of Orthodontics, Department of Oral and Maxillofacial Surgery, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan, 610041, PR China.
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Chen X, Huang X, Zhang X, Chen Z. Metabolism-epigenetic interaction-based bone and dental regeneration: From impacts and mechanisms to treatment potential. Bone 2025; 192:117382. [PMID: 39730093 DOI: 10.1016/j.bone.2024.117382] [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: 09/05/2024] [Revised: 12/11/2024] [Accepted: 12/23/2024] [Indexed: 12/29/2024]
Abstract
Metabolic pathways exhibit fluctuating activities during bone and dental loss and defects, suggesting a regulated metabolic plasticity. Skeletal remodeling is an energy-demanding process related to altered metabolic activities. These metabolic changes are frequently associated with epigenetic modifications, including variations in the expression or activity of enzymes modified through epigenetic mechanisms, which directly or indirectly impact cellular metabolism. Metabolic reprogramming driven by bone and dental conditions alters the epigenetic landscape by modulating the activities of DNA and histone modification enzymes at the metabolite level. Epigenetic mechanisms modulate the expression of metabolic genes, consequently influencing the metabolome. The interplay between epigenetics and metabolomics is crucial in maintaining bone and dental homeostasis by preserving cell proliferation and pluripotency. This review, therefore, aims to examine the effects of metabolic reprogramming in bone and dental-related cells on the regulation of epigenetic modifications, particularly acetylation, methylation, and lactylation. We also discuss the effects of chromatin-modifying enzymes on metabolism and the potential therapeutic benefits of dietary compounds as epigenetic modulators. In this review, we highlight the inconsistencies in current research findings and suggest potential approaches to translate fundamental insights into clinical treatments for bone and tooth diseases.
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Affiliation(s)
- Xinyi Chen
- Stomatology Hospital, School of Stomatology, Zhejiang University School of Medicine, Zhejiang Provincial Clinical Research Centre for Oral Diseases, Key Laboratory of Oral Biomedical Research of Zhejiang Province, Cancer Centre of Zhejiang University, Engineering Research Center of Oral Biomaterials and Devices of Zhejiang Province, Hangzhou 310000, China
| | - Xiaoyuan Huang
- Stomatology Hospital, School of Stomatology, Zhejiang University School of Medicine, Zhejiang Provincial Clinical Research Centre for Oral Diseases, Key Laboratory of Oral Biomedical Research of Zhejiang Province, Cancer Centre of Zhejiang University, Engineering Research Center of Oral Biomaterials and Devices of Zhejiang Province, Hangzhou 310000, China
| | - Xiatong Zhang
- Stomatology Hospital, School of Stomatology, Zhejiang University School of Medicine, Zhejiang Provincial Clinical Research Centre for Oral Diseases, Key Laboratory of Oral Biomedical Research of Zhejiang Province, Cancer Centre of Zhejiang University, Engineering Research Center of Oral Biomaterials and Devices of Zhejiang Province, Hangzhou 310000, China
| | - Zhuo Chen
- Stomatology Hospital, School of Stomatology, Zhejiang University School of Medicine, Zhejiang Provincial Clinical Research Centre for Oral Diseases, Key Laboratory of Oral Biomedical Research of Zhejiang Province, Cancer Centre of Zhejiang University, Engineering Research Center of Oral Biomaterials and Devices of Zhejiang Province, Hangzhou 310000, China.
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Li Y, Guo X, Yao H, Zhang Z, Zhao H. Epigenetic control of dental stem cells: progress and prospects in multidirectional differentiation. Epigenetics Chromatin 2024; 17:37. [PMID: 39623487 PMCID: PMC11613947 DOI: 10.1186/s13072-024-00563-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/29/2024] [Accepted: 11/26/2024] [Indexed: 12/06/2024] Open
Abstract
Dental stem cells, with their exceptional proliferative capacity and multidirectional differentiation potential, hold significant promise for dental and oral tissue regeneration. Epigenetic inheritance, which involves stable and heritable changes in gene expression and function without alterations to the DNA sequence, plays a critical role in numerous biological processes. Environmental factors are particularly influential in epigenetic inheritance, as variations in exposure can lead to changes in epigenetic modifications that subsequently impact gene expression. Epigenetic mechanisms are widely involved in processes such as bone homeostasis, embryogenesis, stem cell fate determination, and disease development. Recently, the epigenetic regulation of dental stem cells has attracted considerable research attention. This paper reviews studies focused on the epigenetic mechanisms governing the multidirectional differentiation of dental stem cells.
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Affiliation(s)
- Yan Li
- Hospital of Stomatology, Jilin University, Changchun, 130021, China
| | - Xinwei Guo
- Department of Stomatology, The First Affiliated Hospital, Zhejiang University, Hangzhou, China
| | - Hua Yao
- Department of Stomatology, The First Affiliated Hospital, Zhejiang University, Hangzhou, China
| | - Zhimin Zhang
- Hospital of Stomatology, Jilin University, Changchun, 130021, China.
| | - Hongyan Zhao
- Hospital of Stomatology, Jilin University, Changchun, 130021, China.
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Sukpaita T, Chirachanchai S, Chanamuangkon T, Pimkhaokham A, Ampornaramveth RS. Alveolar ridge preservation in rat tooth extraction model by chitosan-derived epigenetic modulation scaffold. J Prosthodont Res 2024; 68:299-309. [PMID: 37438120 DOI: 10.2186/jpr.jpr_d_23_00006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 07/14/2023]
Abstract
PURPOSE Alveolar ridge preservation is a surgical technique used to prevent dimensional changes in the alveolar bone by dressing biomaterials in the extraction socket. Recently, a chitosan biphasic calcium phosphate loaded with trichostatin A (CS/BCP/TSA) scaffold was introduced as an excellent bone-regeneration material. This study aimed to explore the biological properties of released trichostatin A (TSA) and evaluate the potential of the CS/BCP/TSA scaffold in preserving the alveolar ridge in a rat tooth extraction model. METHODS In vitro biocompatibility, histone deacetylase (HDAC) activity, and osteogenic differentiation of MC3T3-E1 cells were tested. For in vivo studies, the maxillary first molars (M1) of Wistar rats were extracted, and alveolar ridge preservation was performed using a CS/BCP/TSA scaffold or commercial bone graft. Micro-Computed Tomography (micro-CT), polyfluorochrome labeling, and histological analysis were used to evaluate the ridge-preservation ability. RESULTS The released TSA was cytocompatible. Inhibition of histone deacetylase (HDAC) activity and induction of osteogenic differentiation in MC3T3-E1 cells were confirmed. The socket dressing with the CS/BCP/TSA scaffold showed increased socket bone fill and preserved the buccal and middle aspects of the alveolar ridge compared with the conventional graft. Further analysis of the bone regeneration ability by histomorphometric and histological analyses demonstrated that CS/BCP/TSA showed a significantly higher potential to induce bone formation and complete healing in the extraction socket than the other groups. CONCLUSIONS The CS/BCP/TSA scaffold is a novel candidate for alveolar ridge preservation.
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Affiliation(s)
- Teerawat Sukpaita
- Center of Excellence on Oral Microbiology and Immunology, Faculty of Dentistry, Chulalongkorn University, Bangkok, Thailand
- Department of Oral Surgery, Faculty of Dentistry, Naresuan University, Phitsanulok, Thailand
| | - Suwabun Chirachanchai
- Bioresources Advanced Materials (B2A), The Petroleum and Petrochemical College, Chulalongkorn University, Bangkok, Thailand
- Center of Excellence on Petrochemical and Materials Technology, Chulalongkorn University, Bangkok, Thailand
| | - Theerapat Chanamuangkon
- Biomaterial Testing Center, Faculty of Dentistry, Chulalongkorn University, Bangkok, Thailand
| | - Atiphan Pimkhaokham
- Bioresources Advanced Materials (B2A), The Petroleum and Petrochemical College, Chulalongkorn University, Bangkok, Thailand
- Department of Oral and Maxillofacial Surgery, Faculty of Dentistry, Chulalongkorn University, Bangkok, Thailand
| | - Ruchanee Salingcarnboriboon Ampornaramveth
- Center of Excellence on Oral Microbiology and Immunology, Faculty of Dentistry, Chulalongkorn University, Bangkok, Thailand
- Department of Microbiology, Faculty of Dentistry, Chulalongkorn University, Bangkok, Thailand
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Fontes PK, Dos Santos EC, da Rocha HC, de Lima CB, Milazzotto MP. Metabolic stressful environment drives epigenetic modifications in oviduct epithelial cells. Theriogenology 2024; 215:151-157. [PMID: 38070214 DOI: 10.1016/j.theriogenology.2023.11.025] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/24/2023] [Revised: 11/22/2023] [Accepted: 11/22/2023] [Indexed: 01/06/2024]
Abstract
The oviduct provides a suitable microenvironment from the gametes' final maturation until initial embryo development. Dynamic functional changes are observed in the oviduct cells, mainly controlled by steroid hormones and well-orchestrated during the estrous cycle. However, based on the roles played by the oviduct, additional layers of complexity might be present in its regulatory process. There is a cellular process that includes metabolic adaptation that can guide molecular modifications. This process is known as metaboloepigenetics. Therefore, we aimed to better understand how this crosstalk occurs in oviductal epithelial cells (OEC). Due to limited in situ access to the oviduct, we used the primary in vitro cell culture as a culture model and glucose as a metabolic disturbed factor. For that, cells derived from the oviductal epithelial layer were collected from cows at either follicular or luteal stages (n = 4 animals per group). They were cultured on a monolayer culture system under normoglycemic (2.7 mM glucose) or hyperglycemic conditions (27 mM glucose). On day five of culture, attached cells were submitted to analysis of mitochondrial metabolism (mitochondrial membrane potential - MMP) and epigenetics markers (5- methylcytosine - 5 mC and histone 3 lysine 9 acetylation - H3K9ac). Moreover, the culture media were submitted to the metabolites analysis profile by Raman spectrometry. Data were analyzed considering the effect of glucose level (normoglycemic vs. hyperglycemic), stages when OEC were harvested (follicular vs. luteal), and their interaction (glucose level * cycle stage) by two-way ANOVA. As a result, the high glucose level decreased the H3K9ac and MMP levels but did not affect the 5 mC. Regardless of the metabolic profile of the culture media, the glucose level was the only factor that changed the Raman shifts abundance. Although this present study evaluated oviductal epithelial cells after being submitted to an in vitro monolayer culture system, which is known to lead to cell dedifferentiation, yet, these results provide evidence of a relationship between epigenetic reprogramming and energy metabolism under these cell culture conditions. In conclusion, the levels of metabolites in culture media may be crucial for cellular function and differentiation, meaning that it should be considered in studies culturing oviductal cells.
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Affiliation(s)
- Patricia Kubo Fontes
- Laboratory of Embryonic Metabolism and Epigenetic, Center of Natural and Human Science, Federal University of ABC, Santo André, São Paulo, Brazil
| | - Erika Cristina Dos Santos
- Laboratory of Embryonic Metabolism and Epigenetic, Center of Natural and Human Science, Federal University of ABC, Santo André, São Paulo, Brazil
| | - Heloise Cale da Rocha
- Laboratory of Embryonic Metabolism and Epigenetic, Center of Natural and Human Science, Federal University of ABC, Santo André, São Paulo, Brazil
| | - Camila Bruna de Lima
- Département des Sciences Animales, Centre de Recherche en Reproduction, Développement et Santé Intergénérationnelle, Faculté des Sciences de l'Agriculture et de l'Alimentation, Université Laval, Quebec, Canada
| | - Marcella Pecora Milazzotto
- Laboratory of Embryonic Metabolism and Epigenetic, Center of Natural and Human Science, Federal University of ABC, Santo André, São Paulo, Brazil.
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Chen H, Huang Z, Chen C. The Role of Histone Acetylation Modification in Dental Tissue-Derived Mesenchymal Stem Cells and Odontogenesis. Cell Reprogram 2023; 25:11-19. [PMID: 36594932 DOI: 10.1089/cell.2022.0091] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/04/2023] Open
Abstract
Odontogenesis is a complex physiological process that is based on dental tissue-derived mesenchymal stem cells (MSCs). Dental tissue-derived MSCs are the stem cell populations isolated and characterized from different parts of the oral cavity, and are considered as promising candidates for stem cell-based therapy. During odontogenesis, epigenetic factors can influence the proliferation, differentiation, or apoptosis of dental tissue-derived MSCs. As one of the epigenetic modifications, histone acetylation modification is critical for the proper regulation of many biological processes, including transcriptional regulation of cell cycle progression and cell fate. In odontogenesis, histone acetylation and deacetylation play crucial roles in odontogenic differentiation of dental tissue-derived MSCs. In this review, we aim to outline the general features of acetylation modification and describe their roles in odontogenic differentiation of dental tissue-derived MSCs, as well as their future implications in the field of novel regenerative therapies for the dentine-pulp complex.
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Affiliation(s)
- Haoling Chen
- Department of Pediatric Dentistry, Stomatological Hospital, Southern Medical University, Guangzhou, China
| | - Zijing Huang
- Department of Endodontics, Stomatological Hospital, Southern Medical University, Guangzhou, China
| | - Chuxiao Chen
- Organ Transplant Center, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
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7
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Liaw A, Liu C, Ivanovski S, Han P. The Relevance of DNA Methylation and Histone Modification in Periodontitis: A Scoping Review. Cells 2022; 11:3211. [PMID: 36291079 PMCID: PMC9601099 DOI: 10.3390/cells11203211] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/19/2022] [Revised: 10/03/2022] [Accepted: 10/10/2022] [Indexed: 11/16/2022] Open
Abstract
Background: Periodontitis is a chronic inflammatory disease involving an interplay between bacteria, inflammation, host response genes, and environmental factors. The manifestation of epigenetic factors during periodontitis pathogenesis and periodontal inflammation is still not well understood, with limited reviews on histone modification with periodontitis management. This scoping review aims to evaluate current evidence of global and specific DNA methylation and histone modification in periodontitis and discuss the gaps and implications for future research and clinical practice. Methods: A scoping literature search of three electronic databases was performed in SCOPUS, MEDLINE (PubMed) and EMBASE. As epigenetics in periodontitis is an emerging research field, a scoping review was conducted to identify the extent of studies available and describe the overall context and applicability of these results. Results: Overall, 30 studies were evaluated, and the findings confirmed that epigenetic changes in periodontitis comprise specific modifications to DNA methylation patterns and histone proteins modification, which can either dampen or promote the inflammatory response to bacterial challenge. Conclusions: The plasticity of epigenetic modifications has implications for the future development of targeted epi-drugs and diagnostic tools in periodontitis. Such advances could be invaluable for the early detection and monitoring of susceptible individuals.
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Affiliation(s)
- Andrew Liaw
- Center for Oral-facial Regeneration, Rehabilitation and Reconstruction (COR3), The University of Queensland, Brisbane, QLD 4006, Australia
- School of Dentistry, Faculty of Health and Behavioural Sciences, The University of Queensland, Brisbane, QLD 4006, Australia
| | - Chun Liu
- Center for Oral-facial Regeneration, Rehabilitation and Reconstruction (COR3), The University of Queensland, Brisbane, QLD 4006, Australia
- School of Dentistry, Faculty of Health and Behavioural Sciences, The University of Queensland, Brisbane, QLD 4006, Australia
| | - Sašo Ivanovski
- Center for Oral-facial Regeneration, Rehabilitation and Reconstruction (COR3), The University of Queensland, Brisbane, QLD 4006, Australia
- School of Dentistry, Faculty of Health and Behavioural Sciences, The University of Queensland, Brisbane, QLD 4006, Australia
| | - Pingping Han
- Center for Oral-facial Regeneration, Rehabilitation and Reconstruction (COR3), The University of Queensland, Brisbane, QLD 4006, Australia
- School of Dentistry, Faculty of Health and Behavioural Sciences, The University of Queensland, Brisbane, QLD 4006, Australia
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Larsson L, Kavanagh NM, Nguyen TVN, Castilho RM, Berglundh T, Giannobile WV. Influence of epigenetics on periodontitis and peri-implantitis pathogenesis. Periodontol 2000 2022; 90:125-137. [PMID: 35913702 DOI: 10.1111/prd.12453] [Citation(s) in RCA: 34] [Impact Index Per Article: 11.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/27/2022]
Abstract
Periodontitis is a disease characterized by tooth-associated microbial biofilms that drive chronic inflammation and destruction of periodontal-supporting tissues. In some individuals, disease progression can lead to tooth loss. A similar condition can occur around dental implants in the form of peri-implantitis. The immune response to bacterial challenges is not only influenced by genetic factors, but also by environmental factors. Epigenetics involves the study of gene function independent of changes to the DNA sequence and its associated proteins, and represents a critical link between genetic and environmental factors. Epigenetic modifications have been shown to contribute to the progression of several diseases, including chronic inflammatory diseases like periodontitis and peri-implantitis. This review aims to present the latest findings on epigenetic influences on periodontitis and to discuss potential mechanisms that may influence peri-implantitis, given the paucity of information currently available.
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Affiliation(s)
- Lena Larsson
- Department of Periodontics and Oral Medicine, University of Michigan School of Dentistry, Ann Arbor, Michigan, USA.,Department of Periodontology, Institute of Odontology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
| | - Nolan M Kavanagh
- Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA
| | - Trang V N Nguyen
- Department of Periodontics and Oral Medicine, University of Michigan School of Dentistry, Ann Arbor, Michigan, USA
| | - Rogerio M Castilho
- Department of Periodontics and Oral Medicine and Laboratory of Epithelial Biology, University of Michigan School of Dentistry, Ann Arbor, Michigan, USA
| | - Tord Berglundh
- Department of Periodontology, Institute of Odontology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
| | - William V Giannobile
- Department of Oral Medicine, Infection and Immunity, Harvard School of Dental Medicine, Boston, Massachusetts, USA
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DNA Methylation and Histone Modification in Dental-derived Mesenchymal Stem Cells. Stem Cell Rev Rep 2022; 18:2797-2816. [PMID: 35896859 DOI: 10.1007/s12015-022-10413-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 06/13/2022] [Indexed: 10/16/2022]
Abstract
Epigenetic regulation, mainly involving DNA methylation, histone modification, and noncoding RNAs (ncRNAs), is essential for the regulation of multiple cellular processes. Dental-derived mesenchymal stem cells (DMSCs), a kind of multipotent cells derived from dental tissues, are impactful in regenerative medicine. Recent studies have shown that epigenetic regulation plays a major role in DMSCs. Therefore, exploring how epigenetic regulation is involved in DMSCs may be of guiding significance for tissue repair and regeneration or for exploring more effective treatments. A number of research of ncRNAs in DMSCs have been reported. However, little is known about the roles of DNA methylation and histone modifications in DMSCs. In this review, we summarize the important roles of DNA methylation and histone modifications of the fate of DMSCs.
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10
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Wang F, Xia D, Wang S, Gu R, Yang F, Zhao X, Liu X, Zhu Y, Liu H, Xu Y, Liu Y, Zhou Y. Photocrosslinkable Col/PCL/Mg composite membrane providing spatiotemporal maintenance and positive osteogenetic effects during guided bone regeneration. Bioact Mater 2022; 13:53-63. [PMID: 35224291 PMCID: PMC8844648 DOI: 10.1016/j.bioactmat.2021.10.019] [Citation(s) in RCA: 18] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/19/2021] [Revised: 09/28/2021] [Accepted: 10/15/2021] [Indexed: 02/06/2023] Open
Abstract
Guided bone regeneration membranes have been effectively applied in oral implantology to repair bone defects. However, typical resorbable membranes composed of collagen (Col) have insufficient mechanical properties and high degradation rate, while non-resorbable membranes need secondary surgery. Herein, we designed a photocrosslinkable collagen/polycaprolactone methacryloyl/magnesium (Col/PCLMA/Mg) composite membrane that provided spatiotemporal support effect after photocrosslinking. Magnesium particles were added to the PCLMA solution and Col/PCLMA and Col/PCLMA/Mg membranes were developed; Col membranes and PCL membranes were used as controls. After photocrosslinking, an interpenetrating polymer network was observed by scanning electron microscopy (SEM) in Col/PCL and Col/PCL/Mg membranes. The elastic modulus, swelling behavior, cytotoxicity, cell attachment, and cell proliferation of the membranes were evaluated. Degradation behavior in vivo and in vitro was monitored according to mass change and by SEM. The membranes were implanted into calvarial bone defects of rats for 8 weeks. The Col/PCL and Col/PCL/Mg membranes displayed much higher elastic modulus (p < 0.05), and a lower swelling rate (p < 0.05), than Col membranes, and there were no differences in cell biocompatibility among groups (p > 0.05). The Col/PCL and Col/PCL/Mg membranes had lower degradation rates than the Col membranes, both in vivo and in vitro (p < 0.05). The Col/PCL/Mg groups showed enhanced osteogenic capability compared with the Col groups at week 8 (p < 0.05). The Col/PCL/Mg composite membrane represents a new strategy to display space maintenance and enhance osteogenic potential, which meets clinical needs.
Photocrosslinked Col/PCL and Col/PCL/Mg membranes displayed good mechanical support to provide space for bone regeneration. Col/PCL and Col/PCL/Mg membranes had suitable degradation rates for the maintenance duration of bone regeneration. Photocrosslinked Col/PCL/Mg membranes enhanced osteogenesis and expedited the formation of high-quality bone on week 8.
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11
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Man K, Joukhdar H, Manz XD, Brunet MY, Jiang LH, Rnjak-Kovacina J, Yang XB. Bone tissue engineering using 3D silk scaffolds and human dental pulp stromal cells epigenetic reprogrammed with the selective histone deacetylase inhibitor MI192. Cell Tissue Res 2022; 388:565-581. [PMID: 35362831 PMCID: PMC9110470 DOI: 10.1007/s00441-022-03613-0] [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: 12/08/2021] [Accepted: 03/11/2022] [Indexed: 11/30/2022]
Abstract
Epigenetics plays a critical role in regulating mesenchymal stem cells’ (MSCs) fate for tissue repair and regeneration. There is increasing evidence that the inhibition of histone deacetylase (HDAC) isoform 3 can enhance MSC osteogenesis. This study investigated the potential of using a selective HDAC2 and 3 inhibitor, MI192, to promote human dental pulp stromal cells (hDPSCs) bone-like tissue formation in vitro and in vivo within porous Bombyx Mori silk scaffolds. Both 2 and 5 wt% silk scaffolds were fabricated and characterised. The 5 wt% scaffolds possess thicker internal lamellae, reduced scaffold swelling and degradation rates, whilst increased compressive modulus in comparison to the 2 wt% silk scaffold. MI192 pre-treatment of hDPSCs on 5 wt% silk scaffold significantly enhanced hDPSCs alkaline phosphatase activity (ALP). The expression of osteoblast-related genes (RUNX2, ALP, Col1a, OCN) was significantly upregulated in the MI192 pre-treated cells. Histological analysis confirmed that the MI192 pre-treated hDPSCs-silk scaffold constructs promoted bone extracellular matrix (ALP, Col1a, OCN) deposition and mineralisation compared to the untreated group. Following 6 weeks of subcutaneous implantation in nude mice, the MI192 pre-treated hDPSCs-silk scaffold constructs enhanced the vascularisation and extracellular matrix mineralisation compared to untreated control. In conclusion, these findings demonstrate the potential of using epigenetic reprogramming and silk scaffolds to promote hDPSCs bone formation efficacy, which provides evidence for clinical translation of this technology for bone augmentation.
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Affiliation(s)
- Kenny Man
- Biomaterials & Tissue Engineering Group, School of Dentistry, University of Leeds, WTBB, St. James's University Hospital, Leeds, LS97TF, UK.,School of Chemical Engineering, University of Birmingham, Birmingham, UK
| | - Habib Joukhdar
- Graduate School of Biomedical Engineering, University of New South Wales, Sydney, Australia
| | - Xue D Manz
- Graduate School of Biomedical Engineering, University of New South Wales, Sydney, Australia.,Department of Pulmonary Medicine, Amsterdam UMC, VU University Medical Centre, Amsterdam, The Netherlands
| | - Mathieu Y Brunet
- School of Chemical Engineering, University of Birmingham, Birmingham, UK
| | - Lin-Hua Jiang
- School of Biomedical Sciences, University of Leeds, Leeds, UK
| | - Jelena Rnjak-Kovacina
- Graduate School of Biomedical Engineering, University of New South Wales, Sydney, Australia
| | - Xuebin B Yang
- Biomaterials & Tissue Engineering Group, School of Dentistry, University of Leeds, WTBB, St. James's University Hospital, Leeds, LS97TF, UK.
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12
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Chang CC, Lee KL, Chan TS, Chung CC, Liang YC. Histone Deacetylase Inhibitors Downregulate Calcium Pyrophosphate Crystal Formation in Human Articular Chondrocytes. Int J Mol Sci 2022; 23:ijms23052604. [PMID: 35269745 PMCID: PMC8910507 DOI: 10.3390/ijms23052604] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/29/2022] [Revised: 02/22/2022] [Accepted: 02/24/2022] [Indexed: 11/17/2022] Open
Abstract
Calcium pyrophosphate (CPP) deposition disease (CPPD) is a form of CPP crystal-induced arthritis. A high concentration of extracellular pyrophosphate (ePPi) in synovial fluid is positively correlated with the formation of CPP crystals, and ePPi can be upregulated by ankylosis human (ANKH) and ectonucleotide pyrophosphatase 1 (ENPP1) and downregulated by tissue non-specific alkaline phosphatase (TNAP). However, there is currently no drug that eliminates CPP crystals. We explored the effects of the histone deacetylase (HDAC) inhibitors (HDACis) trichostatin A (TSA) and vorinostat (SAHA) on CPP formation. Transforming growth factor (TGF)-β1-treated human primary cultured articular chondrocytes (HC-a cells) were used to increase ePPi and CPP formation, which were determined by pyrophosphate assay and CPP crystal staining assay, respectively. Artificial substrates thymidine 5′-monophosphate p-nitrophenyl ester (p-NpTMP) and p-nitrophenyl phosphate (p-NPP) were used to estimate ENPP1 and TNAP activities, respectively. The HDACis TSA and SAHA significantly reduced mRNA and protein expressions of ANKH and ENPP1 but increased TNAP expression in a dose-dependent manner in HC-a cells. Further results demonstrated that TSA and SAHA decreased ENPP1 activity, increased TNAP activity, and limited levels of ePPi and CPP. As expected, both TSA and SAHA significantly increased the acetylation of histones 3 and 4 but failed to block Smad-2 phosphorylation induced by TGF-β1. These results suggest that HDACis prevented the formation of CPP by regulating ANKH, ENPP1, and TNAP expressions and can possibly be developed as a potential drug to treat or prevent CPPD.
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Affiliation(s)
- Chi-Ching Chang
- Division of Allergy, Immunology and Rheumatology, Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei 11031, Taiwan;
- Division of Rheumatology, Immunology and Allergy, Department of Internal Medicine, Taipei Medical University Hospital, Taipei 11031, Taiwan
| | - Kun-Lin Lee
- School of Medical Laboratory Science and Biotechnology, College of Medical Science and Technology, Taipei Medical University, Taipei 11031, Taiwan; (K.-L.L.); (C.-C.C.)
- Ph.D. Program in Medical Biotechnology, College of Medical Science and Technology, Taipei Medical University, Taipei 11031, Taiwan
| | - Tze-Sian Chan
- Division of Gastroenterology, Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei 11031, Taiwan;
- Division of Gastroenterology, Department of Internal Medicine, Wan Fang Hospital, Taipei 11696, Taiwan
| | - Chia-Chen Chung
- School of Medical Laboratory Science and Biotechnology, College of Medical Science and Technology, Taipei Medical University, Taipei 11031, Taiwan; (K.-L.L.); (C.-C.C.)
- Ph.D. Program in Medical Biotechnology, College of Medical Science and Technology, Taipei Medical University, Taipei 11031, Taiwan
| | - Yu-Chih Liang
- School of Medical Laboratory Science and Biotechnology, College of Medical Science and Technology, Taipei Medical University, Taipei 11031, Taiwan; (K.-L.L.); (C.-C.C.)
- Ph.D. Program in Medical Biotechnology, College of Medical Science and Technology, Taipei Medical University, Taipei 11031, Taiwan
- Ph.D. Program in Drug Discovery and Development Industry, College of Pharmacy, Taipei Medical University, Taipei 11031, Taiwan
- Traditional Herbal Medicine Research Center, Taipei Medical University Hospital, Taipei 11031, Taiwan
- Correspondence:
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13
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Xiao J, Zheng Y, Zhang W, Zhang Y, Cao P, Liang Y, Bao L, Shi S, Feng X. General Control Nonrepressed Protein 5 Modulates Odontogenic Differentiation Through NF-κB Pathway in Tumor Necrosis Factor-α-Mediated Impaired Human Dental Pulp Stem Cells. Cell Reprogram 2022; 24:95-104. [PMID: 35172106 DOI: 10.1089/cell.2021.0113] [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: 12/23/2022] Open
Abstract
Dental pulp stem cells (DPSCs) from pulpitis patients showed defective osteogenic differentiation. However, as the most well-studied histone acetyltransferase, the impaired general control nonrepressed protein 5 (GCN5) plays essential roles in various developmental processes. The aim of this study was to investigate the effect of GCN5 on DPSCs odontogenic differentiation. The healthy dental pulp tissues were obtained from the extracted impacted third molar of patients with the informed consent. DPSCs were treated with a high concentration of tumor necrosis factor-alpha (TNF-α) (100 ng/mL) and odontogenic differentiation-related gene and GCN5 protein level by Western blot analysis. Proliferation of the DPSCs was evaluated using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Immunofluorescence staining detected GCN5 and NF-κB signaling for p-p65. The mechanism of GCN5 regulating odontogenic differentiation of DPSCs was determined by small interfering RNA analysis. Our data suggested that TNF-α can significantly reduce mineralization and the expression of dentin matrix acidic phosphoprotein 1 and dentin sialophosphoprotein at higher concentration (100 ng/mL). Meanwhile, it showed that the inflammation in microenvironment resulted in a downregulation of GCN5 expression and GCN5 knockdown caused decreased odontogenic differentiation of DPSCs was also found. In addition, the knockdown of GCN5 increased the expression of phosphorylation of p65, thus activating NF-κB pathway of DPSCs. Meanwhile, NF-κB pathway inhibitor pyrrolidinedithiocarbamic acid reversed the siGCN5 decreased odontogenic differentiation of DPSCs. Altogether, our findings indicated that in inflammatory microenvironments GCN5 plays a protective role in pulpitis impaired odontogenic differentiation of DPSCs by activating NF-κB pathway, which may provide a potential approach to dentin regeneration.
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Affiliation(s)
- Jingwen Xiao
- Department of Stomatology, Haimen District People's Hospital, Nantong, China
| | - Ya Zheng
- Nanjing Stomatological Hospital, Medical School of Nanjing University, Nanjing, China
| | - Wei Zhang
- Department of Stomatology, Affiliated Hospital of Nantong University, Nantong University, Nantong, China
| | - Ye Zhang
- Jiangsu Vocational College of Medicine, Yancheng, China
| | - Peipei Cao
- Nantong Boyue Dentistry Out-patient Department, Nantong, China
| | - Yi Liang
- Department of Stomatology, Shanghai East Hospital Affiliated with Tongji University, Shanghai, China
| | - Liuliu Bao
- Department of Stomatology, Affiliated Hospital of Nantong University, Nantong University, Nantong, China
| | - Suping Shi
- Department of Stomatology, Haimen District People's Hospital, Nantong, China
| | - Xingmei Feng
- Department of Stomatology, Affiliated Hospital of Nantong University, Nantong University, Nantong, China
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14
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Man K, Mekhileri NV, Lim KS, Jiang LH, Woodfield TBF, Yang XB. MI192 induced epigenetic reprogramming enhances the therapeutic efficacy of human bone marrows stromal cells for bone regeneration. Bone 2021; 153:116138. [PMID: 34339909 DOI: 10.1016/j.bone.2021.116138] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/04/2021] [Revised: 07/21/2021] [Accepted: 07/27/2021] [Indexed: 12/14/2022]
Abstract
Human bone marrow stromal cells (hBMSCs) have been extensively utilised for bone tissue engineering applications. However, they are associated with limitations that hinder their clinical utility for bone regeneration. Cell fate can be modulated via altering their epigenetic functionality. Inhibiting histone deacetylase (HDAC) enzymes have been reported to promote osteogenic differentiation, with HDAC3 activity shown to be causatively associated with osteogenesis. Therefore, this study aimed to investigate the potential of using an HDAC2 & 3 selective inhibitor - MI192 to induce epigenetic reprogramming of hBMSCs and enhance its therapeutic efficacy for bone formation. Treatment with MI192 caused a time-dose dependant reduction in hBMSCs viability. MI192 was also found to substantially alter hBMSCs epigenetic function through reduced HDAC activity and increased histone acetylation. hBMSCs were pre-treated with MI192 (50 μM) for 48 h prior to osteogenic induction. MI192 pre-treatment significantly upregulated osteoblast-related gene/protein expression (Runx2, ALP, Col1a and OCN) and enhanced alkaline phosphatase specific activity (ALPSA) (1.43-fold) (P ≤ 0.001). Moreover, MI192 substantially increased hBMSCs extracellular matrix calcium deposition (1.4-fold) (P ≤ 0.001) and mineralisation when compared to the untreated control. In 3D microtissue culture, MI192 significantly promoted hBMSCs osteoblast-related gene expression and ALPSA (> 2.41-fold) (P ≤ 0.001). Importantly, MI192 substantially enhanced extracellular matrix deposition (ALP, Col1a, OCN) and mineralisation (1.67-fold) (P ≤ 0.001) within the bioassembled-microtissue (BMT) construct. Following 8-week intraperitoneal implantation within nude mice, MI192 treated hBMSCs exhibited enhanced extracellular matrix deposition and mineralisation (2.39-fold) (P ≤ 0.001) within the BMT when compared to the untreated BMT construct. Taken together, these results demonstrate that MI192 effectively altered hBMSCs epigenetic functionality and is capable of promoting hBMSCs osteogenic differentiation in vitro and in vivo, indicating the potential of using epigenetic reprogramming to enhance the therapeutic efficacy of hBMSCs for bone augmentation strategies.
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Affiliation(s)
- Kenny Man
- Biomaterial and Tissue Engineering Group, School of Dentistry, University of Leeds, Leeds, UK; School of Chemical Engineering, University of Birmingham, Birmingham, UK
| | - Naveen V Mekhileri
- CReaTE Group, Department of Orthopaedic Surgery, University of Otago, Christchurch, New Zealand
| | - Khoon S Lim
- CReaTE Group, Department of Orthopaedic Surgery, University of Otago, Christchurch, New Zealand
| | - Lin-Hua Jiang
- School of Biomedical Sciences, University of Leeds, Leeds, UK
| | - Tim B F Woodfield
- CReaTE Group, Department of Orthopaedic Surgery, University of Otago, Christchurch, New Zealand
| | - Xuebin B Yang
- Biomaterial and Tissue Engineering Group, School of Dentistry, University of Leeds, Leeds, UK.
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15
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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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16
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Histone Acetylation in the Epigenetic Regulation of Bone Metabolism and Related Diseases. Stem Cells Int 2021; 2021:8043346. [PMID: 34326880 PMCID: PMC8310436 DOI: 10.1155/2021/8043346] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/14/2021] [Accepted: 07/01/2021] [Indexed: 02/05/2023] Open
Abstract
As the earliest studied epigenetic modification, acetylation has been explored a lot through the years. While bone tissue acts as an indispensable part of body, researches aimed at the relationship between the bone and acetylation became necessary. Some environmental factors like diet may affect the metabolism status that some metabolites especially nicotinamide adenine dinucleotide (NAD) were found able to regulate intracellular histone acetylation in bone metabolism. This review focuses on representing the interaction among acetylation, metabolism, and the bone. The results showed that acetylation connects a lot with bone metabolism, while the explorations about related metabolites like acetyl-CoA or different environmental exposures are still limited. Some acetylation-related therapy methods of bone diseases based on metabolic regulation or epigenetic enzymes were also reviewed.
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17
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Abuna RPF, Almeida LO, Souza ATP, Fernandes RR, Sverzut TFV, Rosa AL, Beloti MM. Osteoporosis and osteoblasts cocultured with adipocytes inhibit osteoblast differentiation by downregulating histone acetylation. J Cell Physiol 2021; 236:3906-3917. [PMID: 33124698 DOI: 10.1002/jcp.30131] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/11/2020] [Revised: 10/14/2020] [Accepted: 10/20/2020] [Indexed: 12/19/2022]
Abstract
Osteoporosis is characterized by decreased bone mass and adipocyte accumulation within the bone marrow that inhibits osteoblast maturation, leading to a high risk of fractures. Thus, we hypothesized that osteoblasts, besides being negatively affected by interacting with adipocytes, reduce the differentiation of neighboring osteoblasts through the same mechanisms that affect osteoblasts under osteoporotic conditions. We investigated the effect of osteoporosis on osteoblast differentiation and the effect of the conditioned medium of osteoblasts cocultured with adipocytes on the differentiation of other osteoblasts. Osteoporosis was induced by orchiectomy in rats and bone marrow mesenchymal stromal cells (MSCs) were differentiated into osteoblasts. Also, the bone marrow and adipose tissue MSCs were obtained from healthy rats and differentiated into osteoblasts and adipocytes, respectively. Messenger RNA expression, in situ alkaline phosphatase activity, and mineralization confirmed the inhibitory effect of osteoporosis on osteoblast differentiation. This harmful effect was mimicked by the in vitro model using the conditioned medium and it was demonstrated that osteoblasts keep the memory of the negative impact of interacting with adipocytes, revealing an unknown mechanism relevant to the osteoporotic bone loss. Finally, we showed the involvement of acetyl-histone 3 (AcH3) in bone homeostasis as its reduction induced by osteoporosis and conditioned medium impaired osteoblast differentiation. The AcH3 involvement was proved by treating osteoblasts with Trichostatin A that recovered the AcH3 expression and osteoblast differentiation capacity in both situations. Together, our findings indicated that AcH3 might be a target for future studies focused on epigenetic-based therapies to treat bone diseases.
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Affiliation(s)
- Rodrigo P F Abuna
- Bone Research Lab, School of Dentistry of Ribeirão Preto, University of São Paulo, Ribeirão Preto, São Paulo, Brazil
| | - Luciana O Almeida
- Bone Research Lab, School of Dentistry of Ribeirão Preto, University of São Paulo, Ribeirão Preto, São Paulo, Brazil
| | - Alann T P Souza
- Bone Research Lab, School of Dentistry of Ribeirão Preto, University of São Paulo, Ribeirão Preto, São Paulo, Brazil
| | - Roger R Fernandes
- Bone Research Lab, School of Dentistry of Ribeirão Preto, University of São Paulo, Ribeirão Preto, São Paulo, Brazil
| | - Thales F V Sverzut
- Bone Research Lab, School of Dentistry of Ribeirão Preto, University of São Paulo, Ribeirão Preto, São Paulo, Brazil
| | - Adalberto L Rosa
- Bone Research Lab, School of Dentistry of Ribeirão Preto, University of São Paulo, Ribeirão Preto, São Paulo, Brazil
| | - Marcio M Beloti
- Bone Research Lab, School of Dentistry of Ribeirão Preto, University of São Paulo, Ribeirão Preto, São Paulo, Brazil
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18
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Li J, Niu C, Jiang Z, Zhang Z, Pan Y, Xing Q, Guo Q, An S, Hu Y, Wang L. Targeted Delivery of Curcumin to Polyethylene-Induced Osteolysis by Magnetically Guided Zoledronate-Anchored Poly Lactic-Co-Glycolic Acid Nanoparticles via Repressing NF-κB Signaling. Front Pharmacol 2020; 11:600156. [PMID: 33343370 PMCID: PMC7747869 DOI: 10.3389/fphar.2020.600156] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/28/2020] [Accepted: 10/28/2020] [Indexed: 12/14/2022] Open
Abstract
Aseptic loosening induced by periprosthetic osteolysis (PPO) is the leading complication of total joint arthroplasty (TJA) and results in patients having to receive revision surgery. However, there is still no efficient drug to prevent or even slow the pathological process. Herein, we report novel dual-targeted, curcumin-loaded Poly lactic-co-glycolic acid nanoparticles (ZSCNPs) to inhibit polyethylene-induced osteolysis. These ZSCNPs have good biocompatibility and excellent bone binding affinity. Under external magnetic field guidance, the ZSCNPs can specifically target osteolytic sites with sustained curcumin release, efficiently suppress the effect of IκB kinase, subsequently inhibit activation of the nuclear factor-kappa B (NF-κB) signaling pathway, and ultimately prevent osteoclast formation and particle-induced osteolysis. Therefore, these novel dual-targeted, drug-loaded nanoparticles could be applied as a useful strategy for targeted treatment of PPO after TJA.
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Affiliation(s)
- Jingyi Li
- Department of Orthopedics, Xiangya Hospital, Central South University, Changsha, China
- Department of Orthopedics, Hunan Engineering Research Center of Biomedical Metal and Ceramic Implants, Xiangya Hospital, Central South University, Changsha, China
| | - Chengcheng Niu
- Department of Ultrasound Diagnosis, Second Xiangya Hospital, Central South University, Changsha, China
- Research Center of Ultrasonography, Second Xiangya Hospital, Central South University, Changsha, China
| | - Zichao Jiang
- Department of Orthopedics, Xiangya Hospital, Central South University, Changsha, China
- Department of Orthopedics, Hunan Engineering Research Center of Biomedical Metal and Ceramic Implants, Xiangya Hospital, Central South University, Changsha, China
| | - Zhen Zhang
- Department of Orthopedics, Xiangya Hospital, Central South University, Changsha, China
- Department of Orthopedics, Hunan Engineering Research Center of Biomedical Metal and Ceramic Implants, Xiangya Hospital, Central South University, Changsha, China
| | - Yixiao Pan
- Department of Orthopedics, Xiangya Hospital, Central South University, Changsha, China
- Department of Orthopedics, Hunan Engineering Research Center of Biomedical Metal and Ceramic Implants, Xiangya Hospital, Central South University, Changsha, China
| | - Qiqi Xing
- Department of Orthopedics, Xiangya Hospital, Central South University, Changsha, China
- Department of Orthopedics, Hunan Engineering Research Center of Biomedical Metal and Ceramic Implants, Xiangya Hospital, Central South University, Changsha, China
| | - Qi Guo
- Department of Orthopedics, Xiangya Hospital, Central South University, Changsha, China
- Department of Orthopedics, Hunan Engineering Research Center of Biomedical Metal and Ceramic Implants, Xiangya Hospital, Central South University, Changsha, China
| | - Senbo An
- Department of Orthopedics, Xiangya Hospital, Central South University, Changsha, China
- Department of Orthopedics, Hunan Engineering Research Center of Biomedical Metal and Ceramic Implants, Xiangya Hospital, Central South University, Changsha, China
| | - Yihe Hu
- Department of Orthopedics, Xiangya Hospital, Central South University, Changsha, China
- Department of Orthopedics, Hunan Engineering Research Center of Biomedical Metal and Ceramic Implants, Xiangya Hospital, Central South University, Changsha, China
| | - Long Wang
- Department of Orthopedics, Xiangya Hospital, Central South University, Changsha, China
- Department of Orthopedics, Hunan Engineering Research Center of Biomedical Metal and Ceramic Implants, Xiangya Hospital, Central South University, Changsha, China
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19
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Abdelaziz D, Hefnawy A, Al-Wakeel E, El-Fallal A, El-Sherbiny IM. New biodegradable nanoparticles-in-nanofibers based membranes for guided periodontal tissue and bone regeneration with enhanced antibacterial activity. J Adv Res 2020; 28:51-62. [PMID: 33364045 PMCID: PMC7753955 DOI: 10.1016/j.jare.2020.06.014] [Citation(s) in RCA: 84] [Impact Index Per Article: 16.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/12/2020] [Revised: 05/12/2020] [Accepted: 06/17/2020] [Indexed: 12/11/2022] Open
Abstract
Introduction Guided tissue regeneration (GTR) and guided bone regeneration (GBR) are commonly used surgical procedures for the repair of damaged periodontal tissues. These procedures include the use of a membrane as barrier to prevent soft tissue ingrowth and to create space for slowly regenerating periodontium and bone. Recent approaches involve the use of membranes/scaffolds based on resorbable materials. These materials provide the advantage of dissolving by time without the need of surgical intervention to remove the scaffolds. Objectives This study aimed at preparing a new series of nanofibrous scaffolds for GTR/GBR applications with enhanced mechanical properties, cell adhesion, biocompatibility and antibacterial properties. Methods Electrospun nanofibrous scaffolds based on polylactic acid/cellulose acetate (PLA/CA) or poly(caprolactone) (PCL) polymers were prepared and characterized. Different concentrations of green-synthesized silver nanoparticles, AgNPs (1-2% w/v) and hydroxyapatite nanoparticles, HANPs (10-20% w/v) were incorporated into the scaffolds to enhance the antibacterial and bone regeneration activity. Results In-vitro studies showed that addition of HANPs improved the cell viability by around 50% for both types of nanofibrous scaffolds. The tensile properties were also improved through addition of 10% HANPs but deteriorated upon increasing the concentration to 20%. AgNPs significantly improved the antibacterial activity with 40 mm inhibition zone after 32 days. Additionally, the nanofibrous scaffolds showed a desirable degradation profile with losing around 40-70% of its mass in 8 weeks. Conclusions The obtained results show that the developed nanofibrous membranes are promising scaffolds for both GTR and GBR applications.
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Affiliation(s)
- Dina Abdelaziz
- Center for Materials Science (CMS), Zewail City of Science and Technology, 6th of October, Giza 12578, Egypt.,Department of Dental Biomaterials, Faculty of Dentistry, Mansoura University, Egypt
| | - Amr Hefnawy
- Center for Materials Science (CMS), Zewail City of Science and Technology, 6th of October, Giza 12578, Egypt
| | - Essam Al-Wakeel
- Department of Dental Biomaterials, Faculty of Dentistry, Mansoura University, Egypt
| | - Abeer El-Fallal
- Department of Dental Biomaterials, Faculty of Dentistry, Mansoura University, Egypt.,Department of Dental Biomaterials, Faculty of Oral and Dental Medicine, Delta University for Science and Technology, Egypt
| | - Ibrahim M El-Sherbiny
- Center for Materials Science (CMS), Zewail City of Science and Technology, 6th of October, Giza 12578, Egypt
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20
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Human Adipose-Derived Mesenchymal Stem Cells-Incorporated Silk Fibroin as a Potential Bio-Scaffold in Guiding Bone Regeneration. Polymers (Basel) 2020; 12:polym12040853. [PMID: 32272682 PMCID: PMC7240549 DOI: 10.3390/polym12040853] [Citation(s) in RCA: 21] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2020] [Revised: 04/02/2020] [Accepted: 04/05/2020] [Indexed: 02/07/2023] Open
Abstract
Recently, stem cell-based bone tissue engineering (BTE) has been recognized as a preferable and clinically significant strategy for bone repair. In this study, a pure 3D silk fibroin (SF) scaffold was fabricated as a BTE material using a lyophilization method. We aimed to investigate the efficacy of the SF scaffold with and without seeded human adipose-derived mesenchymal stem cells (hASCs) in facilitating bone regeneration. The effectiveness of the SF-hASCs scaffold was evaluated based on physical characterization, biocompatibility, osteogenic differentiation in vitro, and bone regeneration in critical rat calvarial defects in vivo. The SF scaffold demonstrated superior biocompatibility and significantly promoted osteogenic differentiation of hASCs in vitro. At six and twelve weeks postimplantation, micro-CT showed no statistical difference in new bone formation amongst all groups. However, histological staining results revealed that the SF-hASCs scaffold exhibited a better bone extracellular matrix deposition in the defect regions compared to other groups. Immunohistochemical staining confirmed this result; expression of osteoblast-related genes (BMP-2, COL1a1, and OCN) with the SF-hASCs scaffold treatment was remarkably positive, indicating their ability to achieve effective bone remodeling. Thus, these findings demonstrate that SF can serve as a potential carrier for stem cells, to be used as an osteoconductive bioscaffold for BTE applications.
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21
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Chen R, Ren L, Cai Q, Zou Y, Fu Q, Ma Y. The role of epigenetic modifications in the osteogenic differentiation of adipose-derived stem cells. Connect Tissue Res 2019; 60:507-520. [PMID: 31203665 DOI: 10.1080/03008207.2019.1593395] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
Over the last decade, stem cells have drawn extensive attention from scientists due to their full potential in tissue engineering, gene therapy, and cell therapy. Adipose-derived stem cells (ADSCs), which represent one type of mesenchymal stem cell (MSC), hold great promise in bone tissue engineering due to their painless collection procedure, their ability to self-renew and their multi-lineage differentiation properties. Major epigenetic mechanisms, which involve DNA methylation, histone modifications and RNA interference (RNAi), are known to represent one of the determining factors of ADSC fate and differentiation. Understanding the epigenetic modifications of ADSCs may provide a clue for improving stem cell therapy in bone repair and regeneration. The aim of this review is to present the recent advances in understanding the epigenetic mechanisms that facilitate ADSC differentiation into an osteogenic lineage, in addition to the characteristics of the main epigenetic modifications.
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Affiliation(s)
- Ruixin Chen
- Department of Prosthodontics, Guanghua School of Stomatology, Hospital of Stomatology, Sun Yat-sen University , Guangzhou , China.,Guangdong Provincial Key Laboratory of Stomatology , Guangzhou , China
| | - Lin Ren
- Department of Prosthodontics, Guanghua School of Stomatology, Hospital of Stomatology, Sun Yat-sen University , Guangzhou , China.,Guangdong Provincial Key Laboratory of Stomatology , Guangzhou , China
| | - Qingwei Cai
- Department of Prosthodontics, Guanghua School of Stomatology, Hospital of Stomatology, Sun Yat-sen University , Guangzhou , China.,Guangdong Provincial Key Laboratory of Stomatology , Guangzhou , China
| | - Yang Zou
- Department of Prosthodontics, Guanghua School of Stomatology, Hospital of Stomatology, Sun Yat-sen University , Guangzhou , China.,Guangdong Provincial Key Laboratory of Stomatology , Guangzhou , China
| | - Qiang Fu
- Department of Prosthodontics, Guanghua School of Stomatology, Hospital of Stomatology, Sun Yat-sen University , Guangzhou , China.,Guangdong Provincial Key Laboratory of Stomatology , Guangzhou , China
| | - Yuanyuan Ma
- Department of Prosthodontics, Guanghua School of Stomatology, Hospital of Stomatology, Sun Yat-sen University , Guangzhou , China.,Guangdong Provincial Key Laboratory of Stomatology , Guangzhou , China
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22
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Sukpaita T, Chirachanchai S, Suwattanachai P, Everts V, Pimkhaokham A, Ampornaramveth RS. In Vivo Bone Regeneration Induced by a Scaffold of Chitosan/Dicarboxylic Acid Seeded with Human Periodontal Ligament Cells. Int J Mol Sci 2019; 20:ijms20194883. [PMID: 31581495 PMCID: PMC6801435 DOI: 10.3390/ijms20194883] [Citation(s) in RCA: 23] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/21/2019] [Revised: 09/25/2019] [Accepted: 09/29/2019] [Indexed: 12/16/2022] Open
Abstract
Chitosan/dicarboxylic acid (CS/DA) scaffold has been developed as a bone tissue engineering material. This study evaluated a CS/DA scaffold with and without seeded primary human periodontal ligament cells (hPDLCs) in its capacity to regenerate bone in calvarial defects of mice. The osteogenic differentiation of hPDLCs was analyzed by bone nodule formation and gene expression. In vivo bone regeneration was analyzed in mice calvarial defects. Eighteen mice were divided into 3 groups: one group with empty defects, one group with defects with CS/DA scaffold, and a group with defects with CS/DA scaffold and with hPDLCs. After 6 and 12 weeks, new bone formation was assessed using microcomputed tomography (Micro-CT) and histology. CS/DA scaffold significantly promoted in vitro osteoblast-related gene expression (RUNX2, OSX, COL1, ALP, and OPN) by hPDLCs. Micro-CT revealed that CS/DA scaffolds significantly promoted in vivo bone regeneration both after 6 and 12 weeks (p < 0.05). Histological examination confirmed these findings. New bone formation was observed in defects with CS/DA scaffold; being similar with and without hPDLCs. CS/DA scaffolds can be used as a bone regenerative material with good osteoinductive/osteoconductive properties.
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Affiliation(s)
- Teerawat Sukpaita
- Research Unit on Oral Microbiology and Immunology, Department of Microbiology, Faculty of Dentistry, Chulalongkorn University, Bangkok 10330, Thailand.
- Department of Oral and Maxillofacial Surgery, Faculty of Dentistry, Chulalongkorn University, Bangkok 10330, Thailand.
| | - Suwabun Chirachanchai
- Center of Excellence on Petrochemical and Materials Technology, Chulalongkorn University, Bangkok 10330, Thailand.
- Bioresources Advanced Materials (B2A), The Petroleum and Petrochemical College, Chulalongkorn University, Bangkok 10330, Thailand.
| | - Pornchanok Suwattanachai
- Bioresources Advanced Materials (B2A), The Petroleum and Petrochemical College, Chulalongkorn University, Bangkok 10330, Thailand.
| | - Vincent Everts
- Department of Oral Cell Biology, Academic Centre for Dentistry Amsterdam (ACTA), University of Amsterdam and VU University Amsterdam, Gustav Mahlerlaan 3004, 1081 LA Amsterdam, The Netherlands.
| | - Atiphan Pimkhaokham
- Department of Oral and Maxillofacial Surgery, Faculty of Dentistry, Chulalongkorn University, Bangkok 10330, Thailand.
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23
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Zhao Q, Ji K, Wang T, Li G, Lu W, Ji J. Effect of the Histone Deacetylases Inhibitors on the Differentiation of Stem Cells in Bone Damage Repairing and Regeneration. Curr Stem Cell Res Ther 2019; 15:24-31. [PMID: 31486757 DOI: 10.2174/1574888x14666190905155516] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/01/2019] [Revised: 07/24/2019] [Accepted: 08/08/2019] [Indexed: 01/02/2023]
Abstract
Tissue damage repairing and regeneration is a research hot topic. Tissue engineering arises at the historic moment which is a defect repair compound composed of seed cells, tissue engineering scaffolds, and inducing factors. Stem cells have a limited growth period in vitro culture, and they have a pattern of replicating ageing, and these disadvantages are limiting the applications of stem cells in basic research and clinical treatment. The enhancement of stem cell differentiation ability is a difficult problem to overcome, and it is possible to enhance the differentiation ability of stem cells through histone modification so as to provide a more robust foundation for damage repairing and regeneration. Studies have shown that Histone Deacetylases (HDAC) inhibitors can improve mesenchymal stem cells in vitro induced in different directions, conversion efficiency, increasing the feasibility and safety of stem cell therapy and tissue engineering, to offer reference to promote the stem cell therapy in clinical application. Therefore, this paper mainly focusing on the usage and achievements of the deacetylase inhibitors in stem cell differentiation studies and their use and prospects in repair of bone tissue defects.
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Affiliation(s)
- Qing Zhao
- Nanjing Stomatological Hospital, Medical School of Nanjing University, Nanjing, China.,Nanjing Key Laboratory, Nanjing Stomatological Hospital, Medical School of Nanjing University, Nanjing, China
| | - Kun Ji
- Nanjing Stomatological Hospital, Medical School of Nanjing University, Nanjing, China
| | - Tiancong Wang
- Nanjing Stomatological Hospital, Medical School of Nanjing University, Nanjing, China
| | - Guifeng Li
- Nanjing Stomatological Hospital, Medical School of Nanjing University, Nanjing, China
| | - Wei Lu
- Nanjing Stomatological Hospital, Medical School of Nanjing University, Nanjing, China
| | - Jun Ji
- Nanjing Stomatological Hospital, Medical School of Nanjing University, Nanjing, China.,Nanjing Key Laboratory, Nanjing Stomatological Hospital, Medical School of Nanjing University, Nanjing, China
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24
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Liu YW, An SB, Yang T, Xiao YJ, Wang L, Hu YH. Protection Effect of Curcumin for Macrophage-Involved Polyethylene Wear Particle-Induced Inflammatory Osteolysis by Increasing the Cholesterol Efflux. Med Sci Monit 2019; 25:10-20. [PMID: 30599093 PMCID: PMC6327781 DOI: 10.12659/msm.914197] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022] Open
Abstract
BACKGROUND Periprosthetic osteolysis, induced by wear particles and inflammation, is a common reason for failure of primary arthroplasty. Curcumin, a nature phenol from plants, has been reported to reduce the inflammation in macrophages. This study aimed to investigate the potential effect of curcumin on macrophage involved, wear particle-induced osteolysis and its mechanism. MATERIAL AND METHODS RAW264.7 macrophages were used to test the effects of polyethylene (PE) particles and curcumin on macrophage cholesterol efflux and phenotypic changes. A mouse model of PE particle-induced calvarial osteolysis was established to test the effects of curcumin in vivo. After 14 days of treatment, the bone quality of the affected areas was analyzed by micro-computed tomography (micro-CT) and histology, and the bone surrounding soft tissues were analyzed at the cellular and molecular levels. RESULTS We found that PE particles can stimulate osteoclastogenesis and produce an M1-like phenotype in macrophages in vitro. Curcumin enhanced the cholesterol efflux in macrophages, and maintained the M0-like phenotype under the influence of PE particles in vitro. Additionally, the cholesterol transmembrane regulators ABCA1, ABCG1, and CAV1 were enhanced by curcumin in vivo. We also found enhanced bone density, reduced osteoclastogenesis, and fewer inflammatory responses in the curcumin treated groups in our mouse osteolysis model. CONCLUSIONS Our study findings indicated that curcumin can inhibit macrophage involved osteolysis and inflammation via promoting cholesterol efflux. Maintaining the cholesterol efflux might be a potential strategy to prevent periprosthetic osteolysis after total joint arthroplasty surgery.
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Affiliation(s)
- Yu-Wei Liu
- Department of Orthopaedics, Xiangya Hospital, Central South University, Changsha, Hunan, China (mainland)
| | - Sen-Bo An
- Department of Orthopaedics, Xiangya Hospital, Central South University, Changsha, Hunan, China (mainland)
| | - Tao Yang
- Department of Orthopaedics, Xiangya Hospital, Central South University, Changsha, Hunan, China (mainland)
| | - Yue-Jun Xiao
- Department of Orthopaedics, Xiangya Hospital, Central South University, Changsha, Hunan, China (mainland)
| | - Long Wang
- Department of Orthopaedics, Xiangya Hospital, Central South University, Changsha, Hunan, China (mainland)
| | - Yi-He Hu
- Department of Orthopaedics, Xiangya Hospital, Central South University, Changsha, Hunan, China (mainland)
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25
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Xiao T, Fu Y, Zhu W, Xu R, Xu L, Zhang P, Du Y, Cheng J, Jiang H. HDAC8, A Potential Therapeutic Target, Regulates Proliferation and Differentiation of Bone Marrow Stromal Cells in Fibrous Dysplasia. Stem Cells Transl Med 2018; 8:148-161. [PMID: 30426726 PMCID: PMC6344909 DOI: 10.1002/sctm.18-0057] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2018] [Revised: 08/06/2018] [Accepted: 08/15/2018] [Indexed: 12/12/2022] Open
Abstract
Fibrous dysplasia (FD) is a disease of postnatal skeletal stem cells caused by activating mutations of guanine nucleotide-binding protein alpha-stimulating activity polypeptide (GNAS). FD is characterized by high proliferation and osteogenesis disorder of bone marrow stromal cells (BMSCs), resulting in bone pain, deformities, and fractures. The cAMP-CREB pathway, which is activated by GNAS mutations, is known to be closely associated with the occurrence of FD. However, so far there is no available targeted therapeutic strategy for FD, as a critical issue that remains largely unknown is how this pathway is involved in FD. Our previous study revealed that histone deacetylase 8 (HDAC8) inhibited the osteogenic differentiation of BMSCs via epigenetic regulation. Here, compared with normal BMSCs, FD BMSCs exhibited significantly high proliferation and weak osteogenic capacity in response to HDAC8 upregulation and tumor protein 53 (TP53) downregulation. Moreover, inhibition of cAMP reduced HDAC8 expression, increased TP53 expression and resulted in the improvement of FD phenotype. Importantly, HDAC8 inhibition prevented cAMP-induced cell phenotype and promoted osteogenesis in nude mice that were implanted with FD BMSCs. Mechanistically, HDAC8 was identified as a transcriptional target gene of CREB1 and its transcription was directly activated by CREB1 in FD BMSCs. In summary, our study reveals that HDAC8 associates with FD phenotype and demonstrates the mechanisms regulated by cAMP-CREB1-HDAC8 pathway. These results provide insights into the molecular regulation of FD pathogenesis, and offer novel clues that small molecule inhibitors targeting HDAC8 are promising clinical treatment for FD. Stem Cells Translational Medicine 2019;8:148&14.
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Affiliation(s)
- Tao Xiao
- Jiangsu Key Laboratory of Oral Diseases, Nanjing Medical University, Nanjing, People's Republic of China.,Department of Oral and Maxillofacial Surgery, Affiliated Hospital of Stomatology, Nanjing Medical University, Nanjing, People's Republic of China
| | - Yu Fu
- Jiangsu Key Laboratory of Oral Diseases, Nanjing Medical University, Nanjing, People's Republic of China.,Department of Oral and Maxillofacial Surgery, Affiliated Hospital of Stomatology, Nanjing Medical University, Nanjing, People's Republic of China
| | - Weiwen Zhu
- Jiangsu Key Laboratory of Oral Diseases, Nanjing Medical University, Nanjing, People's Republic of China
| | - Rongyao Xu
- Jiangsu Key Laboratory of Oral Diseases, Nanjing Medical University, Nanjing, People's Republic of China
| | - Ling Xu
- Jiangsu Key Laboratory of Oral Diseases, Nanjing Medical University, Nanjing, People's Republic of China
| | - Ping Zhang
- Jiangsu Key Laboratory of Oral Diseases, Nanjing Medical University, Nanjing, People's Republic of China.,Department of Oral and Maxillofacial Surgery, Affiliated Hospital of Stomatology, Nanjing Medical University, Nanjing, People's Republic of China
| | - Yifei Du
- Department of Oral and Maxillofacial Surgery, Affiliated Hospital of Stomatology, Nanjing Medical University, Nanjing, People's Republic of China
| | - Jie Cheng
- Jiangsu Key Laboratory of Oral Diseases, Nanjing Medical University, Nanjing, People's Republic of China
| | - Hongbing Jiang
- Jiangsu Key Laboratory of Oral Diseases, Nanjing Medical University, Nanjing, People's Republic of China.,Department of Oral and Maxillofacial Surgery, Affiliated Hospital of Stomatology, Nanjing Medical University, Nanjing, People's Republic of China
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26
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Cengiz IF, Oliveira JM, Reis RL. Micro-CT - a digital 3D microstructural voyage into scaffolds: a systematic review of the reported methods and results. Biomater Res 2018; 22:26. [PMID: 30275969 PMCID: PMC6158835 DOI: 10.1186/s40824-018-0136-8] [Citation(s) in RCA: 58] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/12/2018] [Accepted: 09/03/2018] [Indexed: 01/28/2023] Open
Abstract
BACKGROUND Cell behavior is the key to tissue regeneration. Given the fact that most of the cells used in tissue engineering are anchorage-dependent, their behavior including adhesion, growth, migration, matrix synthesis, and differentiation is related to the design of the scaffolds. Thus, characterization of the scaffolds is highly required. Micro-computed tomography (micro-CT) provides a powerful platform to analyze, visualize, and explore any portion of interest in the scaffold in a 3D fashion without cutting or destroying it with the benefit of almost no sample preparation need. MAIN BODY This review highlights the relationship between the scaffold microstructure and cell behavior, and provides the basics of the micro-CT method. In this work, we also analyzed the original papers that were published in 2016 through a systematic search to address the need for specific improvements in the methods section of the papers including the amount of provided information from the obtained results. CONCLUSION Micro-CT offers a unique microstructural analysis of biomaterials, notwithstanding the associated challenges and limitations. Future studies that will include micro-CT characterization of scaffolds should report the important details of the method, and the derived quantitative and qualitative information can be maximized.
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Affiliation(s)
- Ibrahim Fatih Cengiz
- 3B’s Research Group, I3Bs – Research Institute on Biomaterials, Biodegradables and Biomimetics, University of Minho, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, AvePark, Parque de Ciência e Tecnologia, Zona Industrial da Gandra, Barco, 4805-017 Guimarães, Portugal
- ICVS/3B’s – PT Government Associate Laboratory, Braga/Guimarães, Portugal
| | - Joaquim Miguel Oliveira
- 3B’s Research Group, I3Bs – Research Institute on Biomaterials, Biodegradables and Biomimetics, University of Minho, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, AvePark, Parque de Ciência e Tecnologia, Zona Industrial da Gandra, Barco, 4805-017 Guimarães, Portugal
- ICVS/3B’s – PT Government Associate Laboratory, Braga/Guimarães, Portugal
- The Discoveries Centre for Regenerative and Precision Medicine, Headquarters at University of Minho, AvePark, Parque de Ciência e Tecnologia, Zona Industrial da Gandra, Barco, 4805-017 Guimarães, Portugal
| | - Rui L. Reis
- 3B’s Research Group, I3Bs – Research Institute on Biomaterials, Biodegradables and Biomimetics, University of Minho, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, AvePark, Parque de Ciência e Tecnologia, Zona Industrial da Gandra, Barco, 4805-017 Guimarães, Portugal
- ICVS/3B’s – PT Government Associate Laboratory, Braga/Guimarães, Portugal
- The Discoveries Centre for Regenerative and Precision Medicine, Headquarters at University of Minho, AvePark, Parque de Ciência e Tecnologia, Zona Industrial da Gandra, Barco, 4805-017 Guimarães, Portugal
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27
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Pang Y, Yuan X, Guo J, Wang X, Yang M, Zhu J, Wang J. The effect of liraglutide on the proliferation, migration, and osteogenic differentiation of human periodontal ligament cells. J Periodontal Res 2018; 54:106-114. [DOI: 10.1111/jre.12607] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/21/2017] [Revised: 08/06/2018] [Accepted: 08/08/2018] [Indexed: 12/17/2022]
Affiliation(s)
- Yunqing Pang
- School of StomatologyLanzhou University Lanzhou China
| | - Xuemin Yuan
- School of StomatologyLanzhou University Lanzhou China
| | - Jia Guo
- School of StomatologyLanzhou University Lanzhou China
| | - Xuemei Wang
- School of StomatologyLanzhou University Lanzhou China
| | - Man Yang
- School of StomatologyLanzhou University Lanzhou China
| | - Jingli Zhu
- School of StomatologyLanzhou University Lanzhou China
| | - Jing Wang
- School of StomatologyLanzhou University Lanzhou China
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28
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Huynh NCN, Everts V, Ampornaramveth RS. Histone deacetylases and their roles in mineralized tissue regeneration. Bone Rep 2017; 7:33-40. [PMID: 28856178 PMCID: PMC5565747 DOI: 10.1016/j.bonr.2017.08.001] [Citation(s) in RCA: 45] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/30/2017] [Revised: 04/19/2017] [Accepted: 08/09/2017] [Indexed: 01/18/2023] Open
Abstract
Histone acetylation is an important epigenetic mechanism that controls expression of certain genes. It includes non-sequence-based changes of chromosomal regional structure that can alter the expression of genes. Acetylation of histones is controlled by the activity of two groups of enzymes: the histone acetyltransferases (HATs) and histone deacetylases (HDACs). HDACs remove acetyl groups from the histone tail, which alters its charge and thus promotes compaction of DNA in the nucleosome. HDACs render the chromatin structure into a more compact form of heterochromatin, which makes the genes inaccessible for transcription. By altering the transcriptional activity of bone-associated genes, HDACs control both osteogenesis and osteoclastogenesis. This review presents an overview of the function of HDACs in the modulation of bone formation. Special attention is paid to the use of HDAC inhibitors in mineralized tissue regeneration from cells of dental origin.
HDACs regulate the transcription activity of bone related genes. Inhibition of HDAC promotes osteogenic/odontogenic differentiation. HDAC inhibitors are applicable for mineral tissue regeneration therapy.
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Key Words
- ADSCs, adipose tissue-derived stem cells
- ALP, alkaline phosphatase
- BSP, bone sialoprotein
- Bone regeneration
- COL1, type I collagen
- DMP1, dentin matrix acidic phosphoprotein 1
- DPSCs, dental-derived stem cells
- DSPP, dentin sialophosphoprotein
- Dentin formation
- Epigenetic
- GSK-3, glycogen synthase kinase
- HAT, histone acetyltransferase
- HDAC, histone deacetylase
- Histone acetyltransferase
- Histone deacetylase
- MSCs, mesenchymal stem cells
- NaB, sodium butyrate
- OCN, osteocalcin
- OPN, osteopontin
- PCL/PEG, polycaprolactone/polyethylene glycol
- RUNX2, runt-related transcription factor 2
- SOST, sclerostin
- TGF-β/BMP, transforming growth factor-β/bone morphogenetic protein
- TSA, Trichostatin A
- VPA, valproic acid
- WNT/β-catenin, Wingless-int
- hPDLCs, human periodontal ligament cells
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Affiliation(s)
- Nam Cong-Nhat Huynh
- Department of Dental Basic Sciences, Faculty of Odonto-Stomatology, University of Medicine and Pharmacy at Ho Chi Minh City, Viet Nam
| | - Vincent Everts
- Department of Oral Cell Biology, Academic Centre for Dentistry Amsterdam (ACTA), University of Amsterdam and Vrije Universiteit Amsterdam, Research Institute MOVE, Gustav Mahlerlaan 3004, 1081 LA Amsterdam, The Netherlands
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