New insights into the biology of osteocalcin.
New insights into the biology of osteocalcin.
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DOI：
10.1016/j.bone.2015.05.046
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发表时间：
2016-01
期刊：
影响因子：
4.1
通讯作者：
Riddle RC
中科院分区：
文献类型：
--
作者：
Zoch ML;Clemens TL;Riddle RC
骨钙素是骨中最丰富的蛋白质之一，仅由成骨细胞产生。最初被认为是骨矿化的抑制剂，最近的研究表明骨钙素的作用更广泛，扩展到全身代谢，生殖和认知的调节。循环中羧基化不足的骨钙素受胰岛素调节，在前馈回路中起作用以增加β细胞增殖以及胰岛素产生和分泌，而骨骼肌和脂肪组织通过增加其对胰岛素的敏感性来响应骨钙素。骨钙素还在大脑中起作用，以增加神经递质的产生，并在睾丸中刺激睾酮的产生。骨钙素的至少一种假定受体Gprc6a由脂肪、骨骼肌和睾丸的间质细胞表达，并且似乎介导骨钙素在这些组织中的作用。在这篇综述中，我们总结了这些新的发现，这表明骨钙素的能力，在骨局部和作为激素的功能取决于一种新的翻译后机制，改变骨钙素的亲和力骨基质和生物利用度。
Osteocalcin is among the most abundant proteins in bone and is produced exclusively by osteoblasts. Initially believed to be an inhibitor of bone mineralization, recent studies suggest a broader role for osteocalcin that extends to the regulation of whole body metabolism, reproduction, and cognition. Circulating undercarboxylated osteocalcin, which is regulated by insulin, acts in a feed-forward loop to increase β-cell proliferation as well as insulin production and secretion, while skeletal muscle and adipose tissue respond to osteocalcin by increasing their sensitivity to insulin. Osteocalcin also acts in the brain to increase neurotransmitter production and in the testes to stimulate testosterone production. At least one putative receptor for osteocalcin, Gprc6a, is expressed by adipose, skeletal muscle, and the Leydig cells of the testes and appears to mediate osteocalcin’s effects in these tissues. In this review, we summarize these new discoveries, which suggest that the ability of osteocalcin to function both locally in bone and as a hormone depends on a novel post-translational mechanism that alters osteocalcin’s affinity for the bone matrix and bioavailability.