GDF11 Inhibits Bone Formation by Activating Smad2/3 in Bone Marrow Mesenchymal Stem Cells
GDF11 Inhibits Bone Formation by Activating Smad2/3 in Bone Marrow Mesenchymal Stem Cells
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GDF11 通过激活骨髓间充质干细胞中的 Smad2/3 抑制骨形成
DOI：
10.1007/s00223-016-0173-z
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发表时间：
2016-11-01
影响因子：
4.2
通讯作者：
Luo, Xiang-Hang
中科院分区：
文献类型：
--
作者：
Lu, Qiong;Tu, Man-Li;Luo, Xiang-Hang
生长分化因子11（GDF 11）是转化生长因子β超家族的成员。最近的研究证实，GDF 11在衰老过程中调节脑、骨骼肌和心脏的再生中起重要作用;然而，其在骨代谢中的作用仍不清楚。因此，本研究的目的是确定GDF 11对骨代谢的影响，包括体外和体内的骨形成和骨吸收。我们的结果表明，GDF 11抑制骨髓间充质干细胞在体外的成骨分化。在成骨细胞分化过程中，GDF 11通过诱导SMAD 2/3磷酸化来抑制Runx 2的表达。此外，腹膜内注射GDF 11抑制小鼠骨形成并加速与年龄相关的骨丢失。我们的研究结果还表明，GDF 11在体外和体内对破骨细胞分化或骨吸收没有影响。这些结果为靶向GDF 11治疗年龄相关性骨质疏松症提供了进一步的理论基础。
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.