Karsenty Gerard
Departments of Genetics and Development, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY, USA.
Handb Exp Pharmacol. 2020;262:309-323. doi: 10.1007/164_2020_378.
The alternation of resorption of preexisting bone by the osteoclasts followed by de novo bone formation by osteoblasts is called bone modeling during childhood and bone remodeling during adulthood. A central question raised by this physiological process that is fundamental to longitudinal growth during childhood and adolescence and that is attacked at the other end of life in the context of osteoporosis is to know how it is regulated. This question was rejuvenated in the late 1990s and early 2000s years when the application of mouse genetics made it feasible to test whether there were new endocrine determinants of bone (re)modeling. Addressing this question, taking into account fundamental cell biology features of bone led to the hypothesis that there should be a coordinated control of bone growth/mass, energy metabolism, and reproduction. Testing genetically and molecularly, this hypothesis revealed that, in vivo, the adipocyte-derived hormone leptin is a powerful inhibitor of bone mass accrual following its signaling in the brain. This chapter details the molecular bases and biological relevance of this regulation of bone mass accrual by leptin.
破骨细胞对已有骨组织的吸收，随后成骨细胞进行新骨形成，这一交替过程在儿童期称为骨塑形，在成年期称为骨重塑。这个生理过程对于儿童和青少年的纵向生长至关重要，而在生命的另一端，在骨质疏松症的背景下也会受到影响，由此引发的一个核心问题是了解其如何被调节。在20世纪90年代末和21世纪初，当小鼠遗传学的应用使得测试是否存在骨（再）塑形的新内分泌决定因素变得可行时，这个问题再次受到关注。考虑到骨的基本细胞生物学特征来解决这个问题，得出了一个假说，即应该对骨生长/骨量、能量代谢和生殖进行协调控制。通过遗传学和分子学测试，这个假说表明，在体内，脂肪细胞衍生的激素瘦素在大脑中发出信号后，是骨量积累的有力抑制剂。本章详细介绍了瘦素对骨量积累调节的分子基础和生物学意义。
