A novel member of the calcitonin gene-related peptide family, calcitonin receptor-stimulating peptide, inhibits the formation and activity of osteoclasts.
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.
Notoya
Michitaka
M
Department of Biological Sciences, Tokyo Institute of Technology, Yokohama 226-8501, Kanagawa, Japan.
Arai
Rumiko
R
Katafuchi
Takeshi
T
Minamino
Naoto
N
Hagiwara
Hiromi
H
D000199:Actins / Q000187:drug effects; D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000494:pharmacology*; D000242:Cyclic AMP / Q000096:biosynthesis; D008297:Male; D051379:Mice; D010010:Osteoclasts / Q000187:drug effects* / Q000502:physiology; D010024:Osteoporosis / Q000188:drug therapy; D018003:Receptors, Calcitonin / Q000096:biosynthesis*
D000199:Actins; D018003:Receptors, Calcitonin; D000242:Cyclic AMP; D015740:Calcitonin Gene-Related Peptide