title: Involvement of the Ca²⁺ signaling pathway in osteoprotegerin inhibition of osteoclast differentiation and maturation.
abstract: The purpose of this study was to determine whether the Ca(2+) signaling pathway is involved in the ability of osteoprotegerin (OPG) to inhibit osteoclast differentiation and maturation. RAW264.7 cells were incubated with macrophage colony-stimulating factor (M-CSF) + receptor activator of nuclear factor-κB ligand (RANKL) to stimulate osteoclastogenesis and then treated with different concentrations of OPG, an inhibitor of osteoclast differentiation. The intracellular Ca(2+) concentration [Ca(2+)]i and phosphorylation of Ca2+/calmodulin-dependent protein kinase II (CaMKII) in the different treatment groups were measured by flow cytometry and Western blotting, respectively. The results confirmed that M-CSF + RANKL significantly increased [Ca(2+)]i and CaMKII phosphorylation in osteoclasts (p < 0.01), and that these effects were subsequently decreased by OPG treatment. Exposure to specific inhibitors of the Ca(2+) signaling pathway revealed that these changes varied between the different OPG treatment groups. Findings from the present study indicated that the Ca(2+) signaling pathway is involved in both the regulation of osteoclastogenesis as well as inhibition of osteoclast differentiation and activation by OPG.
authors.affiliation: College of Veterinary Medicine, Yangzhou University, Yangzhou 225009, China.
authors.forename: Yingxiao
authors.initials: Y
authors.lastname: Fu
authors.forename: Jianhong
authors.initials: J
authors.lastname: Gu
authors.forename: Yi
authors.initials: Y
authors.lastname: Wang
authors.forename: Yan
authors.initials: Y
authors.lastname: Yuan
authors.forename: Xuezhong
authors.initials: X
authors.lastname: Liu
authors.forename: Jianchun
authors.initials: J
authors.lastname: Bian
authors.forename: Zong-Ping
authors.initials: ZP
authors.lastname: Liu
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects; D016173:Macrophage Colony-Stimulating Factor / Q000378:metabolism; D051379:Mice; D010010:Osteoclasts / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism*; D053244:Osteoprotegerin / Q000494:pharmacology*; D053245:RANK Ligand / Q000378:metabolism
chemical_list: D053244:Osteoprotegerin; D053245:RANK Ligand; D016173:Macrophage Colony-Stimulating Factor; D002118:Calcium
keywords: Ca²⁺ signaling pathway; osteoclast; osteoclastogenesis; osteoprotegerin