Epigenetic landscape in PPARγ2 in the enhancement of adipogenesis of mouse osteoporotic bone marrow stromal cell

BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE

卷:1852

Article

Zhang, Yongxing¹  Ma, Chao²  Liu, Xuqiang³  Wu, Zhenkai⁴  Yan, Peng¹  Ma, Nan⁵  Fan, Qiming⁶  Zhao, Qinghua¹ 

[1] Shanghai Jiao Tong Univ, Sch Med, Shanghai Peoples Hosp 1, Dept Orthopaed, Shanghai 200080, Peoples R China

[2] XuZhou Cent Hosp, Dept Spine Surg, Xuzhou 221009, Jiangsu, Peoples R China

[3] Nanchang Univ, Affiliated Hosp 1, Dept Orthopaed, Nanchang 330019, Jiangxi, Peoples R China

[4] Shanghai Jiao Tong Univ, Sch Med, Shanghai XinHua Hosp, Dept Pediat Orthopaed, Shanghai 200092, Peoples R China

[5] Univ Rostock, Dept Cardiac Surg, D-18055 Rostock, Germany

[6] Shanghai Jiao Tong Univ, Sch Med, Shanghai Peoples Hosp 9, Dept Orthoped Surg,Shanghai Key Lab Orthoped Impl, Shanghai 200011, Peoples R China

关键词: Osteoporosis;    PPAR gamma;    Adipogenesis;    Epigenetics;    Bone marrow stromal cells;    beta-Catenin;   

DOI  :  10.1016/j.bbadis.2015.08.020

来源: Elsevier

【 摘 要 】

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, PPAR gamma 2 regulatory region DNA hypo-methylation, histone 3 and 4 hyper-acetylation and H3K9 hypodi-methylation were observed. These epigenetic modifications were involved not only in PPAR gamma 2 expression but also in osteoporotic BMSC adipogenic differentiation potential. We also found that Wnt/beta-catenin signal played an important role in the establishment and maintenance of epigenetic modifications at PPAR-gamma 2 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 PPAR gamma 2 as a new target for osteoporosis therapy based on epigenetic mechanisms. (C) 2015 Elsevier B.V. All rights reserved.

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