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The involvement of histone methylation in osteoblastic differentiation of human periosteum‐derived cells cultured in vitro under hypoxic conditions
Authors:Dae‐Kwan Yoon  Ji‐Sung Park  Gyu‐Jin Rho  Hyeon‐Jeong Lee  Iel‐Yong Sung  Jang‐Ho Son  Bong‐Wook Park  Young‐Hoon Kang  Sung‐Hoon Byun  Sun‐Chul Hwang  Dong Kyun Woo  Yeong‐Cheol Cho  June‐Ho Byun
Institution:1. Department of Oral and Maxillofacial Surgery, College of Medicine, Ulsan University Hospital, University of Ulsan, Ulsan, South Korea;2. Department of Theriogenology and Biotechnology, College of Veterinary Medicine, Gyeongsang National University, Jinju, South Korea;3. Department of Oral and Maxillofacial Surgery, Gyeongsang National University School of Medicine, Gyeongsang National University Hospital, Institute of Health Sciences, Gyeongsang National University, Jinju, South Korea;4. Department of Orthopaedic Surgery, Institute of Health Sciences, School of Medicine, Gyeongsang National University, Jinju, South Korea;5. College of Pharmacy and Research Institute of Pharmaceutical Sciences, Gyeongsang National University, Jinju, South Korea
Abstract:Although oxygen concentrations affect the growth and function of mesenchymal stem cells (MSCs), the impact of hypoxia on osteoblastic differentiation is not understood. Likewise, the effect of hypoxia‐induced epigenetic changes on osteoblastic differentiation of MSCs is unknown. The aim of this study was to examine the in vitro hypoxic response of human periosteum‐derived cells (hPDCs). Hypoxia resulted in greater proliferation of hPDCs as compared with those cultured in normoxia. Further, hypoxic conditions yielded decreased expression of apoptosis‐ and senescence‐associated genes by hPDCs. Osteoblast phenotypes of hPDCS were suppressed by hypoxia, as suggested by alkaline phosphatase activity, alizarin red‐S‐positive mineralization, and mRNA expression of osteoblast‐related genes. Chromatin immunoprecipitation assays showed an increased presence of H3K27me3, trimethylation of lysine 27 on histone H3, on the promoter region of bone morphogenetic protein‐2. In addition, mRNA expression of histone lysine demethylase 6B (KDM6B) by hPDCs was significantly decreased in hypoxic conditions. Our results suggest that an increased level of H3K27me3 on the promoter region of bone morphogenetic protein‐2, in combination with downregulation of KDM6B activity, is involved in the suppression of osteogenic phenotypes of hPDCs cultured in hypoxic conditions. Although oxygen tension plays an important role in the viability and maintenance of MSCs in an undifferentiated state, the effect of hypoxia on osteoblastic differentiation of MSCs remains controversial. In addition, evidence regarding the importance of epigenetics in regulating MSCs has been limited. This study was to examine the role hypoxia on osteoblastic differentiation of hPDCs, and we examined whether histone methylation is involved in the observed effect of hypoxia on osteogenic differentiation of hPDCs.
Keywords:epigenetics  histone methylation  hPDCs  hypoxia  osteoblastic differentiation
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