Max Delbrück Center for Molecular Medicine, Robert Rössle Strasse 10, 13125, Berlin, Germany.
CECAD Research Center, University of Cologne, Joseph-Stelzmann-Str. 26, 50931, Cologne, Germany.
Calcif Tissue Int. 2018 Mar;102(3):329-336. doi: 10.1007/s00223-017-0361-5. Epub 2017 Nov 13.
The central nervous system is widely known to exert control over our systemic physiology via several mechanisms including the regulation of skeletal metabolism. Neuronal circuits within the hypothalamus have been shown to impact bone mass via leptin-dependent and independent mechanisms; however, the full extent to which the brain controls bone homeostasis is not known. We previously identified cell adhesion molecule1 (Cadm1) as a regulator of body weight and energy homeostasis via its expression in multiple regions of the brain. Here, we show that loss of Cadm1 expression in excitatory neurons results in increased leptin sensitivity in addition to a concomitant reduction in bone mass. Femoral length, bone mineral content, diaphyseal cross-sectional area, and bone strength were all lower in Cadm1-deficient animals. Conversely, inducing expression of Cadm1 in excitatory neurons decreased leptin sensitivity and increased femoral length, bone mineral content, and diaphyseal cross-sectional area. Together, these results illustrate an essential role for this synaptic protein in the neuronal regulation of skeletal bone metabolism.
中枢神经系统通过多种机制对我们的全身生理学施加控制，包括骨骼代谢的调节。下丘脑内的神经元回路已被证明通过瘦素依赖和非依赖机制影响骨量；然而，大脑控制骨稳态的程度尚不清楚。我们之前通过 Cadm1 在大脑多个区域的表达，鉴定出细胞黏附分子 1（Cadm1）是体重和能量稳态的调节剂。在这里，我们表明兴奋性神经元中 Cadm1 表达的缺失除了伴随的骨量减少之外，还导致瘦素敏感性增加。Cadm1 缺陷动物的股骨长度、骨矿物质含量、骨干横截面积和骨强度均较低。相反，在兴奋性神经元中诱导 Cadm1 的表达降低了瘦素敏感性，增加了股骨长度、骨矿物质含量和骨干横截面积。这些结果共同说明了这种突触蛋白在神经元调节骨骼骨代谢中的重要作用。
