KDM6A promotes chondrogenic differentiation of periodontal ligament stem cells by demethylation of SOX9 |
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| Authors: | Pingting Wang Yanjing Li Tingting Meng Junjiang Zhang Yuanyuan Wei Zhaosong Meng Yunfeng Lin Dayong Liu Lei Sui |
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| Affiliation: | 1. Department of Endodontics & Laboratory for Dental Stem Cells and Endocrine Immunology, Tianjin Medical University School of Stomatology, Tianjin, China;2. Department of Prosthodontics, Tianjin Medical University School of Stomatology, Tianjin, China;3. Department of Oral Maxillofacial Surgery, Tianjin Medical University School of Stomatology, Tianjin, China;4. State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China |
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| Abstract: | Objectives KDM6A has been demonstrated critical in the regulation of cell fates. However, whether KDM6A is involved in cartilage formation remains unclear. In this study, we investigated the role of KDM6A in chondrogenic differentiation of PDLSCs, as well as the underlying epigenetic mechanisms. Methods KDM6A shRNA was transfected into PDLSCs by lentivirus. The chondrogenic differentiation potential of PDLSCs was assessed by Alcian blue staining. Immunofluorescence was performed to demonstrate H3K27me3 and H3K4me3 levels during chondrogenesis. SOX9, Col2a1, ACAN and miRNAs (miR‐29a, miR‐204, miR‐211) were detected by real‐time RT‐PCR. Western blot was performed to evaluate SOX9, H3K27me3 and H3K4me3. Results The production of proteoglycans in PDLSCs was decreased after knockdown of KDM6A. Depletion of KDM6A inhibited the expression of SOX9, Col2a1, ACAN and resulted in increased H3K27me3 and decreased H3K4me3 levels. EZH2 inhibitor rescued the chondrogenic potential of PDLSCs after knockdown of KDM6A by regulating H3K27me3. Additionally, miR‐29a, miR‐204 and miR‐211 were also involved in the process of PDLSCs chondrogenesis. Conclusions KDM6A is required in chondrogenic differentiation of PDLSCs by demethylation of H3K27me3, and EZH2 inhibitor could rescue chondrogenesis of PDLSCs after knockdown of KDM6A. It could be inferred that upregulation of KDM6A or application of EZH2 inhibitor might improve mesenchymal stem cell mediated cartilage regeneration in inflammatory tissue destruction such as osteoarthritis. |
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| Keywords: | chondrogenesis KDM6A periodontal ligment stem cells SOX9 |
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