A novel member of the calcitonin gene-related peptide family, calcitonin receptor-stimulating peptide, inhibits the formation and activity of osteoclasts
A novel member of the calcitonin gene-related peptide family, calcitonin receptor-stimulating peptide, inhibits the formation and activity of osteoclasts
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DOI：
10.1016/j.ejphar.2007.01.034
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发表时间：
2007-04-10
影响因子：
5
通讯作者：
Hagiwara, Hiromi
中科院分区：
文献类型：
--
作者：
Notoya, Michitaka;Arai, Rumiko;Hagiwara, Hiromi
我们从猪脑中分离出一种新的肽，降钙素受体刺激肽-1（CRSP-1），并发现给大鼠施用这种肽可引起血浆钙浓度的短暂降低。因此，我们研究了CRSP-1对破骨细胞生成的影响。破骨细胞样细胞由脾细胞或骨髓细胞通过核因子-κ B配体受体激活剂（RANKL）和巨噬细胞集落刺激因子（M-CSF）的组合形成。CRSP-1剂量依赖性地抑制多核破骨细胞样细胞的形成，降钙素受体抑制剂部分拮抗CRSP-1对破骨细胞形成的抑制。此外，CRSP-1破坏了肌动蛋白环，这是破骨细胞再吸收活性的典型指标;它通过蛋白激酶A的信号通路促成了这一作用。我们的研究结果表明，CRSP-1通过抑制多核破骨细胞的形成和活性来抑制破骨细胞生成。CRSP-1对破骨细胞代谢的抑制作用在程度上与猪降钙素相似。CRSP-1可能为开发用于预防和治疗骨质疏松症的工具提供线索。(c)2007 Elsevier B. V.保留所有权利。
We isolated a novel peptide, calcitonin receptor-stimulating peptide-1 (CRSP-1), from porcine brain and found that the administration of this peptide into rats induced a transient decrease in plasma calcium concentration. Therefore, we investigated the effects of CRSP-1 on osteoclastogenesis. Osteoclast-like cells were formed from spleen cells or bone marrow cells by a combination of the receptor activator of nuclear factor-kappa B ligand (RANKL) and macrophage colony-stimulating factor (M-CSF). CRSP-1 dose-dependently inhibited the formation of multinucleated osteoclast-like cells, and a calcitonin receptor inhibitor antagonized in part the inhibition of osteoclast formation by CRSP-1. Furthermore, CRSP-1 destroyed the actin ring that is a typical index of osteoclast resorption activity; it contributed to this action via the signaling pathway of protein kinase A. Our findings indicate that CRSP-1 inhibits osteoclastogenesis by inhibiting the formation and activity of multinucleated osteoclasts. The inhibitory effects of CRSP-1 on osteoclast metabolism were similar in degree to those of porcine calcitonin. CRSP-1 might provide a clue to the development of tools useful in the prevention and treatment of osteoporosis. (c) 2007 Elsevier B.V. All rights reserved.