Involvement of the Ca2+ signaling pathway in osteoprotegerin inhibition of osteoclast differentiation and maturation.
10.4142/jvs.2015.16.2.151
- Author:
Yingxiao FU
1
;
Jianhong GU
;
Yi WANG
;
Yan YUAN
;
Xuezhong LIU
;
Jianchun BIAN
;
Zong Ping LIU
Author Information
1. College of Veterinary Medicine, Yangzhou University, Yangzhou 225009, China. liuzongping@yzu.edu.cn
- Publication Type:Original Article ; Research Support, Non-U.S. Gov't
- Keywords:
Ca2+ signaling pathway;
osteoclast;
osteoclastogenesis;
osteoprotegerin
- MeSH:
Animals;
Calcium/*metabolism;
*Calcium Signaling;
*Cell Differentiation/drug effects;
Cell Line;
Cell Survival/drug effects;
Gene Expression Regulation/drug effects;
Macrophage Colony-Stimulating Factor/metabolism;
Mice;
Osteoclasts/*cytology/*drug effects/*metabolism;
Osteoprotegerin/*pharmacology;
RANK Ligand/metabolism
- From:Journal of Veterinary Science
2015;16(2):151-156
- CountryRepublic of Korea
- Language:English
-
Abstract:
The purpose of this study was to determine whether the Ca2+ 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-kappaB ligand (RANKL) to stimulate osteoclastogenesis and then treated with different concentrations of OPG, an inhibitor of osteoclast differentiation. The intracellular Ca2+ concentration [Ca2+]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 [Ca2+]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 Ca2+ signaling pathway revealed that these changes varied between the different OPG treatment groups. Findings from the present study indicated that the Ca2+ signaling pathway is involved in both the regulation of osteoclastogenesis as well as inhibition of osteoclast differentiation and activation by OPG.
