Inhibin A is an endocrine stimulator of bone mass and strength
Inhibin A is an endocrine stimulator of bone mass and strength
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DOI：
10.1210/en.2006-0848
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发表时间：
2007-04-01
期刊：
影响因子：
4.8
通讯作者：
Gaddy, Dana
中科院分区：
文献类型：
--
作者：
Perrien, Daniel S.;Akel, Nisreen S.;Gaddy, Dana
性腺功能在骨稳态中起主要作用。人们普遍认为性腺功能减退症的骨骼后果仅仅是由于性类固醇的损失;然而，在血清雌二醇水平降低之前，骨转换的增加开始于围绝经期。这些数据和我们的证明表明，在体外骨细胞分化的急性调节，使我们测试是否在体内调节骨质量的InhA（InhA）。使用可诱导的人InhA表达的转基因模型，InhA增加全身骨矿物质密度，增加骨体积，并改善完整小鼠胫骨近端的生物力学性能，还防止了脊柱和胫骨近端性腺切除术相关的BMD和骨体积和强度的损失。此外，InhA增加矿物质沉积率，双标记表面，血清骨钙素水平在体内和成骨细胞体外不影响破骨细胞的数量或活性。这些结果共同证明了InhA对体内骨骼的新刺激作用。这些研究提供的体内证据表明，性腺因素以外的性类固醇激素在调节骨量和强度发挥重要作用，结合我们以前的临床数据，表明性腺InhA可能是一个正常的内分泌系统的组成部分，调节骨质量的轴向和approxular骨骼。
Gonadal function plays a major role in bone homeostasis. It is widely held that the skeletal consequences of hypogonadism are solely due to a loss of sex steroids; however, increases in bone turnover begin during perimenopause before decreases in serum estradiol levels. These data and our demonstration that inhibins acutely regulate bone cell differentiation in vitro led us to test whether inhibin A (InhA) regulates bone mass in vivo. Using a transgenic model of inducible human InhA expression, InhA increased total body bone mineral density, increased bone volume, and improved biomechanical properties at the proximal tibia in intact mice and also prevented the loss of BMD and bone volume and strength associated with gonadectomy at both the spine and proximal tibia. In addition, InhA increased mineral apposition rate, double-labeled surface, and serum osteocalcin levels in vivo and osteoblastogenesis ex vivo without affecting osteoclast number or activity. Together these results demonstrate novel stimulatory effects of InhA on the skeleton in vivo. These studies provide in vivo evidence demonstrating that gonadal factors other than sex steroids play an important role in regulating bone mass and strength and, combined with our previous clinical data, suggest that gonadal InhA may be a component of the normal endocrine repertoire that regulates bone quality in both the axial and appendicular skeleton.