Pharmacological study on bone metabolism by nervous activity

脊椎动物骨骼中分布着丰富的肾上腺素能和肽能神经末梢，它们在骨重建中起着重要作用。最近研究表明，交感神经活性增加通过骨吸收增加和骨形成减少引起骨丢失。骨吸收增加是基于破骨细胞形成和破骨细胞活性的刺激。我们还证明了人成骨细胞和骨细胞都具有肾上腺素能受体（Ars）和神经肽受体，并且它们组成性表达可扩散的轴突导向分子，已知其作为生长神经纤维的化学引诱剂和/或化学排斥剂。这些发现表明，交感神经和外周感觉神经元的轴突延伸到成骨细胞和成骨细胞是局部骨代谢的动态神经调节所必需的。然而，尽管一些研究表明神经-骨细胞相互作用， ...更多信息 成骨细胞和成骨细胞的活化是否作为对神经元活化的直接反应而发生或需要中间细胞尚不清楚。因此，我们研究了直接的神经成骨细胞通信，通过使用体外共培养模型，包括小鼠成骨细胞，MC 3 T3-El，和神经突喷出小鼠上级颈神经节。加载钙荧光团Fluo-3后，通过共聚焦激光扫描显微镜检查神经突成骨细胞单位。蝎毒（SV）的加入引起神经突活化（即，Ca^2+动员），并在一个滞后期后，成骨细胞Ca^2+动员。SV对不存在神经突的MC 3 T3-E1细胞没有直接影响。加入α1-AR拮抗剂哌唑嗪浓度依赖性地阻止了SV神经激活导致的成骨细胞激活。因此，我们最近的研究结果表明，MC 3 T3-E1的激活（通过Ca^2+动员来判断）可能是与特定激活的神经纤维接触的直接结果。在体外获得的证据表明，神经成骨细胞的串扰可以发生在没有中介转导细胞和去甲肾上腺素是一个重要的调解人，这种通信。最近的几项体内和体外研究表明，通过分别表达α-和β-Ars的成骨细胞和成骨细胞，对骨形成和骨吸收具有拟交感神经作用。少

The vertebrate skeleton is richly innervated with adrenergic and peptidergic nerve terminals, and these play important roles in bone remodelling. Recently showed that increased sympathetic nervous activity causes bone loss via an increase in bone resorption and a decrease in bone formation. Increased bone resorption is based on the stimulation of both osteoclast formation and osteoclast activity. And we also demonstrated that human osteoblastic as well as osteoclastic cells are equipped with adrenergic receptors (Ars) and neuropeptide receptors and that they constitutively express diffusible axon guidance molecules known to function as a chemoattractant and/or chemorepellent for growing nerve fibers. These findings suggest that the extension of axons of sympathetic and peripheral sensory neurons to osteoblastic and osteoclastic cells is required for the dynamic neural regulation of local bone metabolism. However, while several studies have shown a functional nerve-bone cell interplay, … More whether both osteoblastic and osteoclastic cells activation occurs as a direct response to neuronal activation or requires an intermediary cell is unclear. Therefore, we examined direct nerve-osteoblastic cell communication by using an in vitro co-culture model comprising mouse osteoblastic cells, MC3T3-El, and neurite-spouting mouse superior cervical ganglia. Following loading with the calcium fluorophore Fluo-3, neurite-osteoblastic cell units were examined by confocal laser scanning microscopy. The addition of scorpion venom (SV) elicited neurite activation (i.e., Ca^<2+> mobilization) and, after a lag period, osteoblastic Ca^<2+> mobilization. The SV had no direct effect on the MC3T3-El cells in the absence of neurites. The addition of an α1-AR antagonist, prazosin concentration-dependently prevented the osteoblastic activation that resulted as a consequence of the neural activation by SV. Thus, our recent findings demonstrate that MC3T3-E1 activation, as judge by Ca^<2+> mobilization, can be a direct consequence of contact with a specific activated nerve fiber. This evidence obtained in vitro demonstrates that nerve-osteoblastic cell cross-talk can occur in the absence of an intermediary transducing cell and that noradrenaline is an important mediator of this communication. Several recent in vivo and in vitro studies have demonstrated a sympathomimetic action on bone formation and resorption via osteoblastic and osteoclastic cells, respectively, expressing α-and β-Ars. Less