Inhibitory effect of CGRP on osteoclast formation by mouse bone marrow cells treated with isoproterenol.
The present study was designed to elucidate the mode of action of isoproterenol (Isp; adrenergic beta-agonist) and to characterize the effect of the calcitonin gene-related peptide (CGRP; sensory neuropeptide) on osteoclast formation induced by Isp in a mouse bone marrow culture system. Treatment of mouse bone marrow cells with Isp generated tartrate-resistant acid phosphatase (TRAP)-positive multinuclear cells (MNCs) capable of excavating resorptive pits on dentine slices, and caused an increase in receptor activator of NF-kappaB ligand (RANKL) and a decrease in osteoprotegerin (OPG) production by the marrow cells. The osteoclast formation was significantly inhibited by OPG, suggesting the involvement of the RANKL-RANK system. CGRP inhibited the osteoclast formation caused by Isp or soluble RANKL (s-RANKL) but had no influence on RANKL or OPG production by the bone marrow cells treated with Isp, suggesting that CGRP inhibited the osteoclast formation by interfering with the action of RANKL produced by the Isp-treated bone marrow cells without affecting RANKL or OPG production. This in vitro data suggest the physiological interaction of sympathetic and sensory nerves in osteoclastogenesis in vivo.
Ishizuka
Kyoko
K
Department of Pharamacology, School of Dentistry, Aichi-Gakuin University, Nagoya 464-8650, Japan.
Hirukawa
Koji
K
Nakamura
Hiroshi
H
Togari
Akifumi
A
D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000818:Animals; D001854:Bone Marrow Cells / Q000187:drug effects* / Q000502:physiology; D015740:Calcitonin Gene-Related Peptide / Q000494:pharmacology*; D002352:Carrier Proteins / Q000378:metabolism / Q000494:pharmacology; D002452:Cell Count / Q000379:methods; D002478:Cells, Cultured; D004347:Drug Interactions; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D006023:Glycoproteins / Q000378:metabolism / Q000494:pharmacology; D007150:Immunohistochemistry / Q000379:methods; D007545:Isoproterenol / Q000494:pharmacology*; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism / Q000494:pharmacology; D051379:Mice; D010010:Osteoclasts / Q000187:drug effects* / Q000502:physiology; D053244:Osteoprotegerin; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism; D018124:Receptors, Tumor Necrosis Factor
D000318:Adrenergic beta-Agonists; D002352:Carrier Proteins; D006023:Glycoproteins; D008562:Membrane Glycoproteins; D053244:Osteoprotegerin; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; D018160:Receptors, Cytoplasmic and Nuclear; D018124:Receptors, Tumor Necrosis Factor; C505687:Tnfrsf11a protein, mouse; C506031:Tnfrsf11b protein, mouse; C505689:Tnfsf11 protein, mouse; D015740:Calcitonin Gene-Related Peptide; D007545:Isoproterenol