Inhibitory effect of CGRP on osteoclast formation by mouse bone marrow cells treated with isoproterenol

Inhibitory effect of CGRP on osteoclast formation by mouse bone marrow cells treated with isoproterenol
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DOI:
10.1016/j.neulet.2004.12.046
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发表时间:
2005-04-29
影响因子:
2.5
通讯作者:
Togari, A
Togari, A
中科院分区:
医学4区
文献类型:
--
作者:
Ishizuka, K;Hirukawa, K;Togari, A

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本研究旨在阐明异丙肾上腺素(isproterenol,ISP;肾上腺素能P-激动剂)的作用机制,并研究降钙素基因相关肽(CGRP,感觉神经肽)对isp诱导的小鼠骨髓破骨细胞形成的影响。用异丙肾上腺素处理小鼠骨髓细胞产生抗酒石酸酸性磷酸酶(TRAP)阳性的多核细胞(MNC),能够在牙本质切片上挖掘吸收凹陷,并导致骨髓细胞核因子-kappaB受体激活剂(RANKL)增加和骨保护素(OPG)产生减少。OPG明显抑制破骨细胞的形成,提示RANKL-RANK系统参与了破骨细胞的形成。CGRP可抑制isp或可溶性RANKL(S-RANKL)诱导的破骨细胞的形成,但对isp处理的骨髓细胞产生的RANKL或OPG无影响,提示CGRP通过干扰isp处理的骨髓细胞产生的RANKL而抑制破骨细胞的形成,而不影响RANKL或OPG的产生。这一体外数据提示交感神经和感觉神经在体内破骨细胞形成过程中的生理相互作用。(C)2004爱思唯尔爱尔兰有限公司。保留所有权利。
The present study was designed to elucidate the mode of action of isoproterenol (Isp; adrenergic P-agonist) and to characterize the effect of the calcitonin gene-related peptide (CGRP; sensory neuropeptide) on osteoclast formation induced by Isp in a mouse bone marrow culture system. Treatment of mouse bone marrow cells with Isp generated tartrate-resistant acid phosphatase (TRAP)-positive multinuclear cells (MNCs) capable of excavating resorptive pits on dentine slices, and caused an increase in receptor activator of NF-kappa B ligand (RANKL) and a decrease in osteoprotegerin (OPG) production by the marrow cells. The osteoclast formation was significantly inhibited by OPG, suggesting the involvement of the RANKL-RANK system. CGRP inhibited the osteoclast formation caused by Isp or soluble RANKL (s-RANKL) but had no influence on RANKL or OPG production by the bone marrow cells treated with Isp, suggesting that CGRP inhibited the osteoclast formation by interfering with the action of RANKL produced by the Isp-treated bone marrow cells without affecting RANKL or OPG production. This in vitro data suggest the physiological interaction of sympathetic and sensory nerves in osteoclastogenesis in vivo. (c) 2004 Elsevier Ireland Ltd. All rights reserved.