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神经肽P物质（SP）与降钙素基因相关肽（CGRP）在调节骨形态发生蛋白2（BMP2）诱导的骨分化中的相互作用。

Crosstalk between neuropeptides SP and CGRP in regulation of BMP2-induced bone differentiation.

作者信息

Tuzmen Ceren, Campbell Phil G

机构信息

a Department of Biological Sciences , Carnegie Mellon University , Pittsburgh , PA , USA.

b Engineering Research Accelerator , Carnegie Mellon University , Pittsburgh , PA , USA.

出版信息

Connect Tissue Res. 2018 Dec;59(sup1):81-90. doi: 10.1080/03008207.2017.1408604.

DOI:10.1080/03008207.2017.1408604
PMID:29745819
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6448777/
Abstract

AIM OF THE STUDY

The peripheral nervous system is involved in regulation of bone metabolism via sensory and sympathetic innervation. Substance P (SP) and calcitonin gene-related peptide (CGRP) are two sensory neuropeptides that have been associated with regulation of osteogenic differentiation. However, the interaction between SP and CGRP both with each other and the bone morphogenetic protein 2 (BMP2) in regulation of osteogenic differentiation has not been studied. Therefore, the aim of this study was to investigate the interaction between SP and CGRP on BMP2-induced bone differentiation using model progenitor cells.

MATERIALS AND METHODS

C2C12 myoblasts and MC3T3 pre-osteoblasts were treated with SP and CGRP, both individually and in combination, in the presence of BMP2. The effects of the neuropeptides on BMP2-induced osteogenic differentiation were assessed by measuring alkaline phosphatase (ALP) activity, mineralization, and expression of osteogenic markers.

RESULTS

Both SP and CGRP enhanced BMP2 signaling, Runx2 mRNA expression, as well as mineralization in vitro. Co-stimulation with SP and CGRP resulted in down-regulation of BMP2-induced bone differentiation, suggesting potential crosstalk between the two neuropeptides in regulation of BMP2 signaling.

CONCLUSIONS

Based on the results shown here, CGRP can mitigate augmenting effects of SP on BMP2 signaling and the three pathways potentially converge on Runx2 to regulate BMP2-induced bone differentiation.

摘要

研究目的

外周神经系统通过感觉神经和交感神经支配参与骨代谢的调节。P物质（SP）和降钙素基因相关肽（CGRP）是两种与成骨细胞分化调节相关的感觉神经肽。然而，在成骨细胞分化调节中，SP和CGRP之间以及它们与骨形态发生蛋白2（BMP2）之间的相互作用尚未得到研究。因此，本研究的目的是使用模型祖细胞研究SP和CGRP在BMP2诱导的骨分化中的相互作用。

材料和方法

在BMP2存在的情况下，分别或联合用SP和CGRP处理C2C12成肌细胞和MC3T3前成骨细胞。通过测量碱性磷酸酶（ALP）活性、矿化和成骨标志物的表达来评估神经肽对BMP2诱导的成骨细胞分化的影响。

结果

SP和CGRP均增强了BMP2信号、Runx2 mRNA表达以及体外矿化。SP和CGRP共同刺激导致BMP2诱导的骨分化下调，表明这两种神经肽在调节BMP2信号方面可能存在相互作用。

结论

基于此处所示结果，CGRP可减轻SP对BMP2信号的增强作用，这三条途径可能在Runx2上汇聚，以调节BMP2诱导的骨分化。

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