Takeda S, Karsenty G
Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA.
J Bone Miner Metab. 2001;19(3):195-8. doi: 10.1007/s007740170042.
Vertebrates constantly remodel bone to maintain a constant bone mass. Bone remodeling comprises two phases: bone resorption by the osteoclasts followed by bone formation by the osteoblasts. Although the prevailing view about the control of bone remodeling is that it is an autocrine/paracrine phenomenon, the bone resorption arm of bone remodeling is under a tight endocrine control. To date little is known about the regulation of bone formation. We took the observations that gonadal failure favors bone loss and obesity protects from it as an indication that bone mass, body weight, and reproduction could be regulated by the same hormone(s). Leptin is one of these hormones. Leptin inhibits bone formation by the osteoblasts. This function is dominant, and leptin deficiency results in a high bone mass phenotype despite the hypogonadism characterizing these animals. Genetic biochemical and physiological studies demonstrate that leptin inhibits bone formation following its binding to its receptor in the hypothalamus. These results are the first evience that bone remodeling is a hypothalamic process; they imply necessarily that osteoporosis, the most frequent bone remodeling disease, is partly at least a hypothalamic disease. This finding also has therapeutic implications.
脊椎动物不断重塑骨骼以维持恒定的骨量。骨重塑包括两个阶段：破骨细胞进行骨吸收，随后成骨细胞进行骨形成。尽管关于骨重塑控制的主流观点认为它是一种自分泌/旁分泌现象，但骨重塑的骨吸收环节受到严格的内分泌控制。迄今为止，对于骨形成的调节知之甚少。我们观察到性腺功能衰竭会导致骨质流失，而肥胖则可预防骨质流失，这表明骨量、体重和生殖可能受相同激素的调节。瘦素就是其中一种激素。瘦素抑制成骨细胞的骨形成。这一功能占主导地位，尽管这些动物存在性腺功能减退，但瘦素缺乏会导致高骨量表型。遗传、生化和生理学研究表明，瘦素在下丘脑与受体结合后会抑制骨形成。这些结果首次证明骨重塑是一个下丘脑过程；它们必然意味着骨质疏松症（最常见的骨重塑疾病）至少部分是一种下丘脑疾病。这一发现也具有治疗意义。
