The regulation of bone mass by calcium influx propertiesof osteoclasts

破骨细胞钙内流特性对骨量的调节

• 批准号: 22592071
• 负责人: MASUYAMA Ritsuko
• 金额: $ 2.83万
• 依托单位: Nagasaki University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2010
• 资助国家: 日本
• 起止时间: 2010 至 2012
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-22592071/
• 关键词: カルシウムチャンネル; 破骨細胞; カルシウムシグナル; カルシウム; 骨代謝; TRPV4

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.

破骨细胞的分化严重依赖于钙信号。瞬时受体电位香草酸(TRPV)4介导破骨细胞分化后期的钙内流，从而调节钙信号转导。然而，TRPV4活性的系统修饰作用仍有待确定。由于失去了钙/钙调蛋白信号与TRPV4之间的相互作用，TRPV4激活引起的骨丢失被取消。最后，通过蛋白质组学分析研究了TRPV4与钙调蛋白结合区相互作用的调节子。用LC-MS/MS分析鉴定了非肌肉肌球蛋白IIa，与TRPV4共沉淀后的免疫印迹证实了这一点。这些结果表明，TRPV4的激活相互调节钙/钙调素信号，这涉及TRPV4与肌球蛋白IIa的联系，并促进足够的破骨细胞功能。

项目成果

局所でのビタミンD作用と骨ミネラル代謝

局部维生素 D 作用和骨矿物质代谢

• 发表时间: 2012
• 作者: 水谷諭史;小橋基;藤田雅子;美藤純弘;島谷祐一;松尾龍二;増山律子
• 通讯作者: 増山律子

Pyruvate dehydrogenase kinase 4 induces bone loss at unloading by promoting osteoclastogenesis

丙酮酸脱氢酶激酶 4 通过促进破骨细胞生成诱导卸载时骨质流失

• DOI: 10.1016/j.bone.2011.07.012
• 发表时间: 2012
• 期刊: Bone
• 影响因子: 4.1
• 作者: Wang Y;Liu1 W;Masuyama R;Fukuyama R;Ito M;Zhang Q;Komori H;Murakami T;Moriishi T;Miyazaki T;Kitazawa R;Yoshida CA;Kawai Y;Izumi S;Komori T
• 通讯作者: Komori T

Calcium/calmodulin-signaling supports TRPV4 activation in osteoclasts and regulates bone mass

• DOI: 10.1002/jbmr.1629
• 发表时间: 2012-08-01
• 期刊: JOURNAL OF BONE AND MINERAL RESEARCH
• 影响因子: 6.2
• 作者: Masuyama, Ritsuko;Mizuno, Atsuko;Komori, Toshihisa
• 通讯作者: Komori, Toshihisa

骨恒常性の維持における局所カルシウム輸送とビタミンDの役割

局部钙转运和维生素 D 在维持骨稳态中的作用

• 发表时间: 2013
• 期刊: ビタミン
• 作者: Yamamoto K;Kawakubo T;Yasukochi A;Tsukuba T.;増山律子
• 通讯作者: 増山律子