期刊
GENE
卷 557, 期 2, 页码 209-214出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.gene.2014.12.039
关键词
Osteoporosis; GDF11; Osteoblastogenesis; PPAR-gamma
资金
- Discipline Leaders Project of the Shanghai Municipal Pudong New Area Health System [PWRd2012-16]
- National Natural Science Foundation of China [81201367]
- Key Discipline Funding Project of Shanghai Municipal Pudong New Area Health Bureau [PWZx2014-09]
Growth and differentiation factor 11 (GDF11) is a TGF-beta family member that is expressed widely and plays multiple roles, including regulating axial skeletal patterning during development. However, the function of GDF11 in the bone is barely understood. Here we identify GDF11 as a potent regulator of bone homeostasis. GDF11 level is significantly decreased in the plasma and bone marrow of aging mice and mice with osteoporosis. Pharmacologic GDF11 gain of function leads to a striking increase in osteoblastogenesis and inhibits adipogenesis from bone marrow mesenchymal stem cells by altering the gene expression pattern. GDF11 inhibits the activity of the peroxisome proliferator-activated receptor gamma (PPAR-gamma) by promoting its SUMOylation. Therefore, GDF11 is a critical rheostat for bone turnover and a key integrator of bone homeostasis. These results reveal that skeletal fragility may be reduced by chronic GDF11 administration. (C) 2014 Elsevier B.V. All rights reserved.
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