Department of Pathology and Cell Biology, Columbia University Medical Center, New York, NY 10032, USA.
Diabetologia. 2011 Jun;54(6):1291-7. doi: 10.1007/s00125-011-2155-z. Epub 2011 Apr 19.
Bone remodelling, which maintains bone mass constant during adulthood, is an energy-demanding process. This, together with the observation that the adipocyte-derived hormone leptin is a major inhibitor of bone remodelling, led to the hypothesis that bone cells regulate energy metabolism through an endocrine mechanism. Studies to test this hypothesis identified osteocalcin, a hormone secreted by osteoblasts, as a positive regulator of insulin secretion, insulin resistance and energy expenditure. Remarkably, insulin signalling in osteoblasts is a positive regulator of osteocalcin production and activation via its ability to indirectly enhance bone resorption by osteoclasts. In contrast, leptin is a potent inhibitor of osteocalcin function through its effect on the sympathetic tone. Hence, osteocalcin is part of a complex signalling network between bone and the organs more classically associated with the regulation of energy homeostasis, such as the pancreas and adipose tissue. This review summarises the molecular and cellular bases of the present knowledge on osteocalcin biology and discusses the potential relevance of osteocalcin to human metabolism and pathology.
骨重塑在成年期维持骨量恒定，是一个耗能过程。这一点，再加上观察到脂肪细胞衍生的激素瘦素是骨重塑的主要抑制剂，导致了骨细胞通过内分泌机制调节能量代谢的假说。为了验证这一假说而进行的研究确定了骨钙素，一种由成骨细胞分泌的激素，作为胰岛素分泌、胰岛素抵抗和能量消耗的正调节剂。值得注意的是，成骨细胞中的胰岛素信号通过其间接增强破骨细胞骨吸收的能力，成为骨钙素产生和激活的正调节剂。相比之下，瘦素通过对交感神经张力的影响，是骨钙素功能的有效抑制剂。因此，骨钙素是骨与更经典地与能量稳态调节相关的器官之间复杂信号网络的一部分，如胰腺和脂肪组织。本综述总结了目前关于骨钙素生物学的分子和细胞基础，并讨论了骨钙素对人类代谢和病理学的潜在相关性。
