Calcitonin-gene-related peptide stimulates stromal cell osteogenic differentiation and inhibits RANKL induced NF-kappaB activation, osteoclastogenesis and bone resorption.
Calcitonin-gene-related peptide stimulates stromal cell osteogenic differentiation and inhibits RANKL induced NF-kappaB activation, osteoclastogenesis and bone resorption.
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DOI：
10.1016/j.bone.2009.11.029
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发表时间：
2010-05
期刊：
影响因子：
4.1
通讯作者：
Kingery, Wade S.
中科院分区：
文献类型：
--
作者：
Wang, Liping;Shi, Xiaoyou;Zhao, Rong;Halloran, Bernard P.;Clark, David J.;Jacobs, Christopher R.;Kingery, Wade S.
关键词：
此前我们观察到，对大鼠进行辣椒素治疗可抑制感觉神经肽信号传导，同时减少小梁骨形成和骨体积，并增加破骨细胞数量和骨吸收。降钙素基因相关肽（CGRP）是一种神经肽，广泛分布于支配骨骼的感觉神经元中，我们假设 CGRP 信号传导调节骨骼完整性。在这项研究中，我们在体外检查了 CGRP 对基质细胞和骨细胞分化和活性的影响。通过免疫细胞化学染色和实时 PCR 检测小鼠骨髓基质细胞 (BMSC) 和骨髓巨噬细胞 (BMM) 中的 CGRP 受体。使用 BrdU 掺入、PCR 产物、碱性磷酸酶 (ALP) 活性和矿化测定研究 CGRP 对 BMSC 增殖和成骨细胞分化的影响。通过定量抗酒石酸酸性磷酸酶阳性 (TRAP+) 多核细胞、小凹侵蚀面积、TRAP 和组织蛋白酶 K 的 mRNA 水平以及核因子 -κB (NF-κB) 核定位来确定 CGRP 对 BMM 破骨细胞分化和活性的影响。 BMSC、成骨细胞、BMM 和破骨细胞均表达 CGRP 受体。 CGRP (10-10-10-8M) 刺激 BMSC 增殖，上调成骨细胞基因的表达，并增加 BMSC 中的 ALP 活性和矿化。在 BMM 培养物中，CGRP (10-8M) 抑制 NF-κB 受体激活剂配体 (RANKL) 激活 NF-κB。 CGRP 还下调破骨细胞基因，如 TRAP 和组织蛋白酶 K，减少 TRAP+ 细胞的数量，并抑制 RANKL 刺激的 BMM 中的骨吸收活性。这些结果表明，CGRP 信号传导通过直接刺激基质细胞成骨细胞分化和抑制 RANKL 诱导的 NF-κB 激活、破骨细胞生成和骨吸收来维持骨量。
Previously we observed that capsaicin treatment in rats inhibited sensory neuropeptide signaling, with a concurrent reduction in trabecular bone formation and bone volume, and an increase in osteoclast numbers and bone resorption. Calcitonin gene-related peptide (CGRP) is a neuropeptide richly distributed in sensory neurons innervating the skeleton and we postulated that CGRP signaling regulates bone integrity. In this study we examined CGRP effects on stromal and bone cell differentiation and activity in vitro. CGRP receptors were detected by immunocytochemical staining and real time PCR assays in mouse bone marrow stromal cells (BMSCs) and bone marrow macrophages (BMMs). CGRP effects on BMSC proliferation and osteoblastic differentiation were studied using BrdU incorporation, PCR products, alkaline phosphatase (ALP) activity, and mineralization assays. CGRP effects on BMM osteoclastic differentiation and activity were determined by quantifying tartrate-resistant acid phosphatase positive (TRAP+) multinucleated cells, pit erosion area, mRNA levels of TRAP and cathepsin K, and nuclear factor-κB (NF-κB) nuclear localization. BMSCs, osteoblasts, BMMs, and osteoclasts all expressed CGRP receptors. CGRP (10-10-10-8M) stimulated BMSC proliferation, up-regulated the expression of osteoblastic genes, and increased ALP activity and mineralization in the BMSCs. In BMM cultures CGRP (10-8M) inhibited receptor activator of NF-κB ligand (RANKL) activation of NF-κB. CGRP also down-regulated osteoclastic genes like TRAP and cathepsin K, decreased the numbers of TRAP+ cells, and inhibited bone resorption activity in RANKL stimulated BMMs. These results suggest that CGRP signaling maintains bone mass both by directly stimulating stromal cell osteoblastic differentiation and by inhibiting RANKL induced NF-κB activation, osteoclastogenesis, and bone resorption.
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影响因子：
3
作者：
Akopian, A;Demulder, A;Bergmann, P
通讯作者：
Bergmann, P
影响因子：
3.6
作者：
GAMSE, R;LEEMAN, SE;LEMBECK, F
通讯作者：
LEMBECK, F
影响因子：
4
作者：
Liu, F;Malaval, L;Aubin, JE
通讯作者：
Aubin, JE
影响因子：
2.5
作者：
Ishizuka, K;Hirukawa, K;Togari, A
通讯作者：
Togari, A
影响因子：
4
作者：
Granholm, Susanne;Lundberg, Pernilla;Lerner, Ulf H.
通讯作者：
Lerner, Ulf H.