The regulation of bone mass by calcium influx propertiesof osteoclasts

点击翻译按钮获取中文摘要

Osteoclast differentiation is critically dependent on calcium (Ca2+) signaling. Transient receptor potential vaniroid (TRPV) 4, mediates Ca2+ influx in the late stage of osteoclast differentiation, thereby regulates Ca2+ signaling. However, the system-modifying effect of TRPV4 activity remains to be determined. Bone loss due to TRPV4 activation was abrogated by loss of interactions between Ca2+/calmodulin signaling and TRPV4. Finally, modulators of TRPV4 interactions with the calmodulin-binding domain were investigated by proteomic analysis. Non-muscle myosin IIa was then identified by LC-MS/MS analysis, which was confirmed by immunoblotting following coimmunoprecipitation with TRPV4. These results indicate that TRPV4 activation reciprocally regulates Ca2+/calmodulin signaling, which involves an association of TRPV4 with myosin IIa, and promotes sufficient osteoclast function.