title: Epigenetic landscape in PPARγ2 in the enhancement of adipogenesis of mouse osteoporotic bone marrow stromal cell.
abstract: Osteoporosis is one of the most prevalent skeletal system diseases; yet, its pathophysiological mechanisms remain elusive. Adipocytes accumulate remarkably in the bone marrow of osteoporotic patients. The potential processes and molecular mechanisms underlying adipogenesis in osteoporotic BMSCs have attracted significant attention as adipocytes and osteoblasts share common precursor cells. Some environmental factors influence bone mass through epigenetic mechanisms; however, the role of epigenetic modifications in osteoporosis is just beginning to be investigated, and there is still little data regarding their involvement. In the current study, we investigated how epigenetic modifications, including DNA methylation and histone modifications, lead to adipogenesis in the bone marrow during osteoporosis. A glucocorticoid-induced osteoporosis (GIO) mouse model was established, and BMSCs were isolated from the bone marrow. Compared with normal BMSCs, osteoporotic BMSCs had significantly increased adipogenesis potential and decreased osteogenesis potential. In osteoporotic BMSCs, PPARγ2 regulatory region DNA hypo-methylation, histone 3 and 4 hyper-acetylation and H3K9 hypo-di-methylation were observed. These epigenetic modifications were involved not only in PPARγ2 expression but also in osteoporotic BMSC adipogenic differentiation potential. We also found that Wnt/β-catenin signal played an important role in the establishment and maintenance of epigenetic modifications at PPARγ2 promoter in osteoporotic BMSCs. Finally, we inhibited adipogenesis and rescued osteogenesis of osteoporotic BMSCs by modulating those epigenetic modifications. Our study provides a deeper insight into the pathophysiology of osteoporosis and identifies PPARγ2 as a new target for osteoporosis therapy based on epigenetic mechanisms.
authors: Department of Orthopaedics, Shanghai First People's Hospital, School of Medicine, Shanghai JiaoTong University, Shanghai 200080, PR China.
authors: Yongxing
authors: Y
authors: Zhang
authors: Department of Spine Surgery, XuZhou Central Hospital, XuZhou, JiangSu 221009, PR China.
authors: Chao
authors: C
authors: Ma
authors: Department of Orthopaedics, First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi Province 330019, PR China.
authors: Xuqiang
authors: X
authors: Liu
authors: Department of Pediatric Orthopaedics, Shanghai XinHua Hospital, School of Medicine, Shanghai JiaoTong University, Shanghai 200092, PR China.
authors: Zhenkai
authors: Z
authors: Wu
authors: Department of Orthopaedics, Shanghai First People's Hospital, School of Medicine, Shanghai JiaoTong University, Shanghai 200080, PR China.
authors: Peng
authors: P
authors: Yan
authors: Department of Cardiac Surgery, University of Rostock, Schillingallee 35, Germany.
authors: Nan
authors: N
authors: Ma
authors: Shanghai Key Laboratory of Orthopedic Implants, Department of Orthopedic Surgery, Shanghai Ninth People's Hospital, Shanghai JiaoTong University School of Medicine, Shanghai 200011, PR China. Electronic address: chillow@163.com.
authors: Qiming
authors: Q
authors: Fan
authors: Department of Orthopaedics, Shanghai First People's Hospital, School of Medicine, Shanghai JiaoTong University, Shanghai 200080, PR China. Electronic address: sawboneszhao@163.com.
authors: Qinghua
authors: Q
authors: Zhao
keywords: Adipogenesis; Bone marrow stromal cells; Epigenetics; Osteoporosis; PPARγ; β-Catenin