Pharmacological Study on Neural Regulation of Bone Metabolism

在本研究中，使用RT-PCR的mRNA表达的分析表明，人成骨细胞和成骨细胞配备有肾上腺素能受体和神经肽受体，并组成性表达可扩散的轴突导向分子，这表明交感神经元和外周感觉神经元的轴突延伸到这些细胞是必要的局部骨代谢的动态神经调节。已证实肾上腺素能刺激可调节成骨细胞/基质细胞中IL-6、IL-11、环氧合酶-II、ODF/OPGL/TRANCE/RANKL（ODF/RANKL）和OCIF/OPG的表达。众所周知，这些分子参与破骨细胞生成。ODF/RANKL和OCIF/OPG是破骨细胞生成的直接调控分子。为了阐明破骨细胞生成的肾上腺素能调节，我们研究了肾上腺素（Epi）、异丙肾上腺素（Isp）和苯丙氨酸（Phe）对小鼠骨髓细胞形成抗酒石酸酸性磷酸酶（TRACP）阳性多核细胞（MNC）的影响。TRACP阳性MNC的形成刺激Isp或Epi，但不是苯丙氨酸。在OCIF/OPG存在下未观察到Isp诱导的MNC形成，表明ODF/RANKL和OCIF/OPG产生之间的生理平衡对于破骨细胞生成的重要性。从这些结果可以看出，交感神经的活动通过调节骨髓细胞中ODF和OCIF的表达对破骨细胞的生成具有显著的影响。

In the present study, analysis of mRNA expression using RT-PCR demonstrated that human osteoblastic and osteoclastic cells are equipped with adrenergic receptors and neuropeptide receptors and constitutively express diffusible axon guidance molecules, suggesting that the extension of axons of sympathetic and peripheral sensory neurons to these cells is required for the dynamic neural regulation of local bone metabolism. Adrenergic stimulation was demonstrated to modulate the expression of IL-6, IL-11, cyclooxygenase-II, ODF/OPGL/TRANCE/RANKL(ODF/RANKL) and OCIF/OPG in osteoblasts/stromal cells. These molecules are well known to be involved in osteoclastogenesis. Especially, ODF/RANKL and OCIF/OPG are noticed as direct molecules modulating osteoclastogenesis. To elucidate the adrenergic regulation of osteoclastogenesis, we examined the effects of epinephrine (Epi), isoprenaline (Isp) and phenylephrine (Phe) on the formation of tartarate-resistant acid phosphatase(TRACP)-positive multinucleated cell (MNC) from mouse bone marrow cells. TRACP-positive MNC formation were stimulated by Isp or Epi, but not Phe. The MNC formation induced by Isp was not observed in the presence of OCIF/OPG, suggesting the importance of physiological balance between ODF/RANKL and OCIF/OPG productions for osteoclastogenesis. From these results, it may be suggested that the activity of sympathetic nerves has a significant effect on osteoclastogenesis by modulating ODF and OCIF expression in bone marrow cells.