Notoya Michitaka, Arai Rumiko, Katafuchi Takeshi, Minamino Naoto, Hagiwara Hiromi
Department of Biological Sciences, Tokyo Institute of Technology, Yokohama 226-8501, Kanagawa, Japan.
Eur J Pharmacol. 2007 Apr 10;560(2-3):234-9. doi: 10.1016/j.ejphar.2007.01.034. Epub 2007 Feb 1.
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-kappaB 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.
我们从猪脑中分离出一种新型肽，即降钙素受体刺激肽-1（CRSP-1），并发现将该肽注射到大鼠体内会导致血浆钙浓度短暂下降。因此，我们研究了CRSP-1对破骨细胞生成的影响。通过核因子κB受体激活剂配体（RANKL）和巨噬细胞集落刺激因子（M-CSF）的组合，从脾细胞或骨髓细胞中形成破骨细胞样细胞。CRSP-1剂量依赖性地抑制多核破骨细胞样细胞的形成，并且降钙素受体抑制剂部分拮抗CRSP-1对破骨细胞形成的抑制作用。此外，CRSP-1破坏了作为破骨细胞吸收活性典型指标的肌动蛋白环；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有用工具提供线索。
