The regulation of bone mass by calcium influx propertiesof osteoclasts

2012 Fiscal Year Final Research Report

• Project/Area Number: 22592071
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Functional basic dentistry
• Research Institution: Nagasaki University
• Principal Investigator: MASUYAMA Ritsuko 長崎大学, 医歯薬学総合研究科, 准教授 (60297596)
• Co-Investigator(Kenkyū-buntansha): KOMORI Toshihisa 長崎大学, 医歯薬学総合研究科, 教授 (00252677)
• Project Period (FY): 2010 – 2012
• Keywords: カルシウムチャンネル / 破骨細胞

Research Abstract

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.

Research Products

• [Journal Article] 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 (2013)
  • Author(s): 増山律子
  • Journal Title: ビタミン Volume: 87巻 Pages: 38-43
  • Peer Reviewed
• [Journal Article] Pyruvate dehydrogenase kinase 4 induces bone loss at unloading by promoting osteoclastogenesis. (2012)
  • Author(s): Wang Y, Liu 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
  • Journal Title: Bone Volume: vol50 Pages: 409-419
  • Peer Reviewed
• [Journal Article] Calcium/calmodulin-signaling supports TRPV4 activation in osteoclasts and regulates bone mass (2012)
  • Author(s): Masuyama R, Mizuno A, Komori H, Kajiya H, Uekawa A, Kitaura H, Okabe K, Ohyama K, Komori T
  • Journal Title: Journal of Bone andMineral Research Volume: vol27 Pages: 1708-1721
  • Peer Reviewed
• [Journal Article] Normocalcemia is maintained in mice under conditions of calcium malabsorption by vitamin D-induced inhibition of bone mineralization (2012)
  • Author(s): Lieben L, Masuyama R, Torrekens S, Van Looveren R, Schrooten J, Baatsen P, Lafage-Proust MH, Dresselaers T, Feng JQ, Bonewald LF, Meyer MB, Pike JW, Bouillon R, Carmeliet G
  • Journal Title: Journal of Clinical Investigation Volume: vol122 Pages: 1803-1815
  • Peer Reviewed
• [Journal Article] Overexpression of Bcl2 in osteoblasts inhibits osteoblast differentiation and induces osteocyte apoptosis (2011)
  • Author(s): Moriishi T, Maruyama Z, Fukuyama R, Ito M, Miyazaki T, Kitaura H, Ohnishi H, Furuichi T, Kawai Y, Masuyama R, Komori H, Takada K, Kawaguchi H, Komori T
  • Journal Title: PLoS One Volume: vol6 Pages: e27487
  • Peer Reviewed
• [Presentation] Calcium/calmodulin-signaling regulates TRPV4 action by the process supporting myosin IIa association in osteoclasts (2012)
  • Author(s): 増山律子
  • Organizer: 米国骨代謝学会
  • Place of Presentation: ミネアポリス
  • Year and Date: 2012-10-12
• [Presentation] 局所でのビタミンD作用と骨ミネラル代謝 (2012)
  • Author(s): 増山律子
  • Organizer: 日本骨代謝学会
  • Place of Presentation: 東京都
  • Year and Date: 2012-07-21
• [Presentation] 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 (2012)
  • Author(s): 増山律子
  • Organizer: 日本ビタミン学会
  • Place of Presentation: 岐阜市
  • Year and Date: 2012-06-22
• [Presentation] The Importance of Vitamin D Signaling for Calcium and Bone Homeostasis (2011)
  • Author(s): 増山律子
  • Organizer: 日本骨代謝学会
  • Place of Presentation: 大阪
  • Year and Date: 2011-07-29