Department of Pharmacology, School of Dentistry, Aichi-Gakuin University, Nagoya, Japan.
J Pharmacol Sci. 2010;112(2):184-91. doi: 10.1254/jphs.09283fp. Epub 2010 Jan 22.
There is currently great interest in the bone metabolism induced by the sympathetic nerve system. Recently, direct neurite-osteoblastic cell communication was demonstrated using an in vitro co-culture model comprising neurite-sprouting murine superior cervical ganglia and MC3T3-E1 osteoblast-like cells. In the present study, we examined whether the direct nerve-osteoclastic cell communication was present in an in vitro co-culture model comprising cultured murine superior cervical ganglia and mouse osteoclast-like cells. RAW264.7 cells treated with receptor activator of NF-kappaB ligand were used as osteoclast-like cells. We found that the addition of scorpion venom (SV) elicited neurite activation via intracellular Ca(2+) mobilization and, after a lag period, osteoclastic Ca(2+) mobilization in the co-culture. SV did not have any direct effect on the osteoclastic cells in the absence of the neurites. The addition of an alpha(1)-adrenergic receptor (AR) antagonist, prazosin, concentration-dependently prevented the osteoclastic activation that resulted as a consequence of neural activation by SV. We also found that alpha(1)-adrenergic receptor agonists evoked transient Ca(2+) mobilization and gene expression of interleukin-6 in osteoclastic cells. These results demonstrate that osteoclastic activation occurs via alpha(1)-AR in osteoclastic cells as a direct response to neuronal activation.
目前，人们对交感神经系统引起的骨代谢非常感兴趣。最近，通过使用包含神经突发芽的鼠颈上神经节和 MC3T3-E1 成骨样细胞的体外共培养模型，证明了直接的轴突-成骨细胞通讯的存在。在本研究中，我们检查了包含培养的鼠颈上神经节和鼠破骨细胞样细胞的体外共培养模型中是否存在直接的神经-破骨细胞通讯。用核因子-κB 配体受体激活剂处理 RAW264.7 细胞作为破骨细胞样细胞。我们发现，添加蝎子毒液 (SV) 通过细胞内 Ca(2+)动员引发神经突激活，并在潜伏期后引发共培养物中的破骨细胞 Ca(2+)动员。SV 在没有神经突的情况下对破骨细胞没有任何直接影响。α(1)-肾上腺素能受体 (AR) 拮抗剂哌唑嗪的添加浓度依赖性地阻止了由 SV 引起的神经激活导致的破骨细胞激活。我们还发现，α(1)-肾上腺素能受体激动剂引起破骨细胞中短暂的 Ca(2+)动员和白细胞介素-6 的基因表达。这些结果表明，破骨细胞激活是通过破骨细胞中的 α(1)-AR 作为对神经元激活的直接反应发生的。
