GDF11 Inhibits Bone Formation by Activating Smad2/3 in Bone Marrow Mesenchymal Stem Cells

被引：38
|
作者：
Lu, Qiong [1 ,2 ,3 ,4 ]
Tu, Man-Li [1 ,2 ,5 ]
Li, Chang-Jun [1 ,2 ]
Zhang, Li [1 ,2 ]
Jiang, Tie-Jian [6 ]
Liu, Tang [7 ]
Luo, Xiang-Hang [1 ,2 ]
机构：
[1] Cent S Univ, Dept Metab & Endocrinol, Xiangya Hosp 2, Changsha 410011, Hunan, Peoples R China
[2] Cent S Univ, Xiangya Hosp 2, Natl Clin Res Ctr Metab Dis, Changsha 410011, Hunan, Peoples R China
[3] Cent S Univ, Xiangya Hosp 2, Dept Pharm, Changsha 410011, Hunan, Peoples R China
[4] Emory Univ, Dept Radiol & Imaging Sci, Sch Med, Atlanta, GA 30322 USA
[5] Johns Hopkins Univ, Dept Orthopaed Surg, Sch Med, Baltimore, MD 21205 USA
[6] Cent S Univ, Dept Endocrinol, Xiangya Hosp, Changsha 410008, Hunan, Peoples R China
[7] Cent S Univ, Dept Orthopaed Surg, Xiangya Hosp 2, Changsha 410011, Hunan, Peoples R China
来源：
CALCIFIED TISSUE INTERNATIONAL | 2016年 / 99卷 / 05期
关键词：
Growth differentiation factor 11; Osteoblast; Aging; Osteoporosis; Bone marrow mesenchymal stem cells; DIFFERENTIATION FACTOR 11; AGE-RELATED SWITCH; OSTEOBLAST DIFFERENTIATION; TGF-BETA; ADIPOCYTE DIFFERENTIATION; SYSTEMIC FACTORS; SKELETAL-MUSCLE; MICE; REGENERATION; OSTEOPOROSIS;
D O I：
10.1007/s00223-016-0173-z
中图分类号：
R5 [内科学];
学科分类号：
1002 ; 100201 ;
摘要：
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.
引用
收藏
页码：500 / 509
页数：10
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