Department of Internal Medicine, Erasmus University Medical Center's Gravendijkwal 230, 3015 CE Rotterdam, The Netherlands.
Endocrinology. 2012 Aug;153(8):3593-602. doi: 10.1210/en.2012-1277. Epub 2012 Jun 14.
The mutual interplay between energy homeostasis and bone metabolism is an important emerging concept. Ghrelin and leptin antagonize each other in regulating energy balance, but the role of this interaction in bone metabolism is unknown. Using ghrelin receptor and leptin-deficient mice, we show that ghrelin has dual effects on osteoclastogenesis, inhibiting osteoclast progenitors directly and stimulating osteoclastogenesis via a more potent systemic/central pathway. Using mice with combined ghrelin receptor and leptin deficiency, we find that this systemic osteoclastogenic activity is suppressed by leptin, thus balancing the two counterregulatory ghrelin pathways and leading to an unchanged bone structure. With aging, this osteoclastogenic ghrelin pathway is lost, unmasking the direct protective effect of ghrelin on bone structure. In conclusion, we identify a novel regulatory network linking orexigenic and anorectic metabolic factors with bone metabolism that is age dependent.
能量平衡和骨代谢之间的相互作用是一个重要的新兴概念。生长激素释放肽和瘦素在调节能量平衡方面相互拮抗，但这种相互作用在骨代谢中的作用尚不清楚。使用生长激素释放肽受体和瘦素缺陷小鼠，我们表明生长激素对破骨细胞生成有双重作用，直接抑制破骨细胞前体，并通过更有效的全身/中枢途径刺激破骨细胞生成。使用同时缺乏生长激素释放肽受体和瘦素的小鼠，我们发现这种全身破骨细胞生成活性受瘦素抑制，从而平衡两种拮抗的生长激素释放肽途径，并导致骨结构保持不变。随着年龄的增长，这种破骨细胞生成的生长激素释放肽途径丧失，暴露出生长激素对骨结构的直接保护作用。总之，我们确定了一个新的调节网络，将食欲刺激和食欲抑制代谢因子与骨代谢联系起来，且该网络具有年龄依赖性。
