Central control of bone formation
Central control of bone formation
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DOI：
10.1007/s007740170042
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发表时间：
2001-01-01
影响因子：
3.3
通讯作者：
Karsenty, G
中科院分区：
文献类型：
--
作者：
Takeda, S;Karsenty, G
脊椎动物不断重塑骨骼以保持恒定的骨量。骨重塑包括两个阶段：破骨细胞的骨吸收和成骨细胞的骨形成。虽然目前普遍认为骨重塑的控制是一种自分泌/旁分泌的现象，但骨重塑的骨吸收臂受到严格的内分泌控制。迄今为止，人们对骨形成的调控知之甚少。我们观察到性腺功能衰竭会导致骨质流失，而肥胖可以防止骨质流失，这表明骨量、体重和生殖可以由同一种激素调节。瘦素就是其中一种激素。瘦素抑制成骨细胞形成骨。这种功能占主导地位，尽管这些动物具有性腺功能减退的特征，但瘦素缺乏导致高骨量表型。遗传生化和生理研究表明，瘦素与下丘脑受体结合后抑制骨形成。这些结果是骨重塑是下丘脑过程的第一个证据；它们必然暗示骨质疏松症，最常见的骨重塑疾病，至少部分是下丘脑疾病。这一发现也具有治疗意义。
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.