CGRP may regulate bone metabolism through stimulating osteoblast differentiation and inhibiting osteoclast formation
CGRP may regulate bone metabolism through stimulating osteoblast differentiation and inhibiting osteoclast formation
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DOI：
10.3892/mmr.2016.5023
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发表时间：
2016-05-01
影响因子：
3.4
通讯作者：
Yang, Zhenzhou
中科院分区：
文献类型：
--
作者：
He, Haitao;Chai, Jianshen;Yang, Zhenzhou
降钙素基因相关肽(CGRP)是一种神经肽，广泛分布于中枢和外周神经系统。降钙素基因相关肽在成骨细胞相关细胞中作用的许多机制已被提出用于骨生长和新陈代谢。本研究旨在深入研究CGRP对原代成骨细胞骨代谢影响的成骨细胞和破骨细胞相关机制。取新生兔颅骨原代成骨细胞，分别与不同浓度的人降钙素基因相关肽(HCGRP)、hCGRP及hCGRP(8-37)孵育，或不加任何处理作为对照。治疗后检测细胞内钙离子(Ca~(2+))、环磷酸腺苷(CAMP)及成骨细胞分化标志物激活转录因子-4(ATF4)、骨钙素(OC)、核因子-kappa B受体激活剂(RANKL)和骨保护素(OPG)的表达水平。分离的原代成骨细胞碱性磷酸酶染色呈阳性。HCGRP对成骨细胞内瞬时钙离子浓度无明显影响。HCGRP可上调成骨细胞cAMP、ATF4和OPG的表达，下调RANKL的表达，并呈剂量依赖关系。加入hCGRP(8-37)可明显逆转上述作用。本研究结果表明，CGRP不仅促进了成骨细胞的分化，如hCGRP处理的成骨细胞中ATF4和OC的表达水平上调，而且还抑制了OPG/RANKL调节的破骨细胞的生成。CGRP可能通过成骨细胞和破骨细胞相关机制作为骨代谢调节剂，导致成骨细胞形成，继而激活骨形成。
Calcitonin-gene-related peptide (CGRP) is a neuropeptide, which is widely distributed throughout the central and peripheral nervous systems. Numerous mechanisms underlying the action of CGRP in osteoblast-associated cells have been suggested for bone growth and metabolism. The present study was designed to closely investigate the osteoblast-and osteoclast-associated mechanisms of the effect of CGRP administration on bone metabolism in primary osteoblasts. Primary osteoblasts were obtained from newborn rabbit calvaria and incubated with different concentrations of human CGRP (hCGRP), hCGRP and hCGRP (8-37), or without treatment as a control. Intracellular calcium (Ca2+) and cyclic adenosine monophosphate (cAMP) were detected following treatment, as well as the expression levels of osteoblast differentiation markers, including activating transcription factor-4 (ATF4) and osteocalcin (OC), and receptor activator of nuclear factor kappa B ligand (RANKL) and osteoprotegerin (OPG). The isolated primary osteoblasts were found to stain positively for ALP. hCGRP treatment had no significant effect on transient intracellular Ca2+ in the osteoblasts. Treatment of the osteoblasts with hCGRP led to elevations in the expression levels of cAMP, ATF4 and OPG, and downregulation in the expression of RANKL, in a dose-dependent manner. These effects were markedly reversed by the addition of hCGRP (8-37). The results of the present study demonstrated that CGRP administration not only stimulated osteoblast differentiation, as demonstrated by upregulated expression levels of ATF4 and OC in the hCGRP-treated osteoblasts, but also inhibited OPG/RANKL-regulated osteoclastogenesis. CGRP may act as a modulator of bone metabolism through osteoblast and osteoclast-associated mechanisms, which result in osteoblast formation with subsequent activation of bone formation.