Vanderbilt Center for Bone Biology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.
J Bone Miner Res. 2013 Oct;28(10):2136-44. doi: 10.1002/jbmr.1940.
Bone remodeling allows the conservation of normal bone mass despite constant changes in internal and external environments. The adaptation of the skeleton to these various stimuli leads credence to the notion that bone remodeling is a true homeostatic function, and as such is under the control of specific centers in the central nervous system (CNS). Hypothalamic and brainstem centers, as well as the sympathetic nervous system (SNS), have been identified as regulators of bone remodeling. However, the nature of the afferent CNS stimuli that may modulate CNS centers involved in the control of bone remodeling, with the exception of leptin, remains unclear. Based on the partial efficacy of exercise and mechanical stimulation regimens to prevent microgravity-induced bone loss and the known alterations in vestibular functions associated with space flights, we hypothesized that inner ear vestibular signals may contribute to the regulation of bone remodeling. Using an established model of bilateral vestibular lesions and microtomographic and histomorphometric bone analyses, we show here that induction of bilateral vestibular lesion in rats generates significant bone loss, which is restricted to weight-bearing bones and associated with a significant reduction in bone formation, as observed in rats under microgravity conditions. Importantly, this bone loss was not associated with reduced locomotor activity or metabolic abnormalities, was accompanied with molecular signs of increased sympathetic outflow, and could be prevented by the β-blocker propranolol. Collectively, these data suggest that the homeostatic process of bone remodeling has a vestibulosympathetic regulatory component and that vestibular system pathologies might be accompanied by bone fragility.
骨骼重塑使骨骼能够在内部和外部环境不断变化的情况下保持正常的骨量。骨骼对这些各种刺激的适应证实了骨骼重塑是一种真正的动态平衡功能的观点,因此它受到中枢神经系统 (CNS) 中特定中枢的控制。已经确定下丘脑和脑干中枢以及交感神经系统 (SNS) 是骨骼重塑的调节剂。然而,除了瘦素之外,调节可能调节参与骨骼重塑控制的中枢神经系统中心的中枢神经系统传入刺激的性质仍然不清楚。基于运动和机械刺激方案对预防微重力引起的骨质流失的部分效果,以及与太空飞行相关的前庭功能的已知改变,我们假设内耳前庭信号可能有助于骨骼重塑的调节。使用双侧前庭损伤的既定模型以及微断层扫描和组织形态计量学骨骼分析,我们在这里表明,诱导大鼠双侧前庭损伤会导致明显的骨丢失,这种骨丢失仅限于承重骨骼,并与骨形成的显著减少有关,就像在微重力条件下的大鼠一样。重要的是,这种骨丢失与运动活动减少或代谢异常无关,伴随着交感神经流出增加的分子迹象,并且可以被β受体阻滞剂普萘洛尔预防。总之,这些数据表明,骨骼重塑的动态平衡过程具有前庭交感调节成分,并且前庭系统病理学可能伴随着骨脆弱。