Hinoi Eiichi
Laboratory of Molecular Pharmacology, Faculty of Pharmaceutical Sciences, Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa University, Ishikawa, Japan.
Yakugaku Zasshi. 2012;132(6):721-5. doi: 10.1248/yakushi.132.721.
Bone formation and maintenance are sophisticatedly orchestrated through a well-organized and highly regulated mechanism by two distinct cell types; bone-forming osteoblast and bone-resorbing osteoclast. It has been previously established that the adipocyte-derived hormone leptin regulates bone metabolism through the central nervous system and the sympathetic nervous system. We recently identified the osteoblast as the principal cell type in which the sympathetic tone could signal to regulate bone mass by generating and analyzing the cell specific adrenergic receptor deletion mice. The fact that adipocyte-derived hormone regulates bone metabolism implies that the skeleton might exert a feedback control of glucose metabolism. We then revealed that the skeleton acts as an endocrine regulator of energy metabolism through the osteoblast-specific secreted molecule osteocalcin that activates insulin secretion by pancreatic β-cells, insulin sensitivity in fat, liver, and muscle. Moreover, we have recently reported that the sympathetic tone into osteoblast is a pivotal mediator of leptin regulation of insulin secretion by regulating osteocalcin bioactivity. This unexpected functional cross talk between fat, nervous systems, and skeleton illustrates the importance of the skeleton for the regulation of major physiological functions such as glucose homeostasis in vertebrates.
骨形成和维持是由两种不同的细胞类型，即成骨的成骨细胞和吸收骨的破骨细胞，通过一种组织良好且高度调节的机制精心编排的。先前已经确定，脂肪细胞衍生的激素瘦素通过中枢神经系统和交感神经系统调节骨代谢。我们最近通过生成和分析细胞特异性肾上腺素能受体缺失小鼠，确定成骨细胞是交感神经张力可通过其发出信号来调节骨量的主要细胞类型。脂肪细胞衍生的激素调节骨代谢这一事实意味着骨骼可能对葡萄糖代谢发挥反馈控制作用。然后我们发现，骨骼通过成骨细胞特异性分泌分子骨钙素作为能量代谢的内分泌调节因子，骨钙素可激活胰腺β细胞的胰岛素分泌以及脂肪、肝脏和肌肉中的胰岛素敏感性。此外，我们最近报道，通过调节骨钙素的生物活性，进入成骨细胞的交感神经张力是瘦素调节胰岛素分泌的关键介质。脂肪、神经系统和骨骼之间这种意想不到的功能相互作用说明了骨骼在调节脊椎动物主要生理功能（如葡萄糖稳态）中的重要性。
