Zhang Yan, Shao Jin, Wang Zhi, Yang Tieyi, Liu Shuyi, Liu Yue, Fan Xinbing, Ye Weiguang
Department of Orthopaedics, Gongli Hospital of Pudong New Area, Shanghai 200135, China.
Department of Orthopaedics, Gongli Hospital of Pudong New Area, Shanghai 200135, China.
Gene. 2015 Feb 25;557(2):209-14. doi: 10.1016/j.gene.2014.12.039. Epub 2014 Dec 20.
Growth and differentiation factor 11 (GDF11) is a TGF-β 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 γ (PPAR-γ) 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.
生长分化因子11（GDF11）是一种转化生长因子-β（TGF-β）家族成员，其表达广泛并发挥多种作用，包括在发育过程中调节轴向骨骼模式形成。然而，GDF11在骨骼中的功能却鲜为人知。在此，我们确定GDF11是骨稳态的有效调节因子。在衰老小鼠和骨质疏松小鼠的血浆和骨髓中，GDF11水平显著降低。药理学上GDF11功能的获得导致成骨细胞生成显著增加，并通过改变基因表达模式抑制骨髓间充质干细胞的脂肪生成。GDF11通过促进过氧化物酶体增殖物激活受体γ（PPAR-γ）的SUMO化来抑制其活性。因此，GDF11是骨转换的关键调节器和骨稳态的关键整合者。这些结果表明，长期给予GDF11可能会降低骨骼脆性。
