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Growth hormone synergizes with BMP9 in osteogenic differentiation by activating the JAK/STAT/IGF1 pathway in murine multilineage cells
Author(s) -
Huang Enyi,
Zhu Gaohui,
Jiang Wei,
Yang Ke,
Gao Yanhong,
Luo Qing,
Gao JianLi,
Kim Stephanie H,
Liu Xing,
Li Mi,
Shi Qiong,
Hu Ning,
Wang Linyuan,
Liu Hong,
Cui Jing,
Zhang Wenwen,
Li Ruidong,
Chen Xiang,
Kong YuHan,
Zhang Jiye,
Wang Jinhua,
Shen Jikun,
Bi Yang,
Statz Joseph,
He BaiCheng,
Luo Jinyong,
Wang Huicong,
Xiong Feng,
Luu Hue H,
Haydon Rex C,
Yang Li,
He TongChuan
Publication year - 2012
Publication title -
journal of bone and mineral research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.882
H-Index - 241
eISSN - 1523-4681
pISSN - 0884-0431
DOI - 10.1002/jbmr.1622
Subject(s) - downregulation and upregulation , endocrinology , biology , medicine , growth factor , microbiology and biotechnology , gene silencing , bone morphogenetic protein , ectopic expression , progenitor cell , somatotropic cell , cell culture , growth hormone , stem cell , hormone , gene , receptor , biochemistry , genetics
Growth hormone (GH) is usually released by somatotrophs in the anterior pituitary in response to the GH‐releasing hormone and plays an important role in skeleton development and postnatal growth. However, it is unclear if extrapituitary GH exerts any effect on murine multilineage cells (MMCs). MMCs are multipotent progenitors that give rise to several lineages, including bone, cartilage, and fat. We have identified bone morphogenic protein 9 (BMP9) as one of the most osteogenic BMPs in MMCs by regulating a distinct set of downstream mediators. In this study, we find that GH is one of the most significantly upregulated genes by BMP9 in mouse MMCs through expression‐profiling analysis. We confirm that GH is a direct early target of and upregulated by BMP9 signaling. Exogenous GH synergizes with BMP9 on inducing early and late osteogenic markers in MMCs. Furthermore, BMP9 and GH costimulation leads to a significant expansion of growth plate in cultured limb explants. Although GH alone does not induce de novo bone formation in an ectopic bone formation model, BMP9 and GH costimulated MMCs form more mature bone, which can be inhibited by silencing GH expression. The synergistic osteogenic activity between BMP9 and GH can be significantly blunted by JAK/STAT inhibitors, leading to a decrease in GH‐regulated insulin‐like growth factor 1 (IGF1) expression in MMCs. Our results strongly suggest that BMP9 may effectively regulate extrapituitary GH expression in MMCs. Thus, it is conceivable that the BMP9‐GH‐IGF axis may be exploited as an innovative strategy to enhance osteogenesis in regenerative medicine. © 2012 American Society for Bone and Mineral Research.