期刊
CALCIFIED TISSUE INTERNATIONAL
卷 99, 期 5, 页码 500-509出版社
SPRINGER
DOI: 10.1007/s00223-016-0173-z
关键词
Growth differentiation factor 11; Osteoblast; Aging; Osteoporosis; Bone marrow mesenchymal stem cells
资金
- Major International (Regional) Joint Research Project of China National Natural Scientific Foundation (NSFC) [81520108008]
- Distinguished Young Scientists of China National Natural Scientific Foundation [81125006]
- NSFC-Guangdong Joint Project [U1301222]
- China National Natural Scientific Foundation [81570806]
Growth differentiation factor 11 (GDF11) is a member of the transforming growth factor-beta superfamily. Recent studies confirmed that GDF11 plays an important role in regulating the regeneration of brain, skeletal muscle, and heart during aging; however, its role in bone metabolism remains unclear. Thus, the aim of this study was to determine the effects of GDF11 on bone metabolism, including bone formation and bone resorption, both in vitro and in vivo. Our results showed that GDF11 inhibited osteoblastic differentiation of bone marrow mesenchymal stem cells in vitro. Mechanistically, GDF11 repressed Runx2 expression by inducing SMAD2/3 phosphorylation during osteoblast differentiation. Moreover, intraperitoneal injection of GDF11 inhibited bone formation and accelerated age-related bone loss in mice. Our results also showed that GDF11 had no effect on osteoclast differentiation or bone resorption both in vitro and in vivo. These results provide a further rationale for the therapeutic targeting of GDF11 for the treatment of age-related osteoporosis.
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