Roles of Wnt/beta-catenin signaling inhibitors in interactions between muscle and bone

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K07310
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 48020:Physiology-related
• Research Institution: Kindai University
• Principal Investigator: Kawao Naoyuki 近畿大学, 医学部, 講師 (70388510)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: 筋骨連関 / DKK2 / 骨粗鬆症 / サルコペニア

Outline of Final Research Achievements

Myokines, humoral factors secreted from the skeletal muscles, have recently been getting attention as the key factors related to the interactions between muscle and bone. Dickkopf (DKK) 2 is known as an inhibitor of canonical Wnt/β-catenin signaling, and Wnt/β-catenin signaling is crucial for the maintenance of muscle and bone. The present study was performed to investigate the roles of DKK2 in the interactions between muscle and bone in response to mechanical stress in mice. In the present study, we showed that unloading and androgen deficiency enhance DKK2 expression and secretion in the muscles of mice. Dkk2 might be involved in unloading- and androgen deficiency-induced muscle wasting and osteopenia as a myokine linking muscle to bone.

Free Research Field

生理学

Academic Significance and Societal Importance of the Research Achievements

本研究では、メカニカルストレスに応答して骨格筋で発現が変化する新しいマイオカインとして、古典的Wnt-βカテニン経路阻害因子であるDKK2に着目し、筋と骨のネットワークの視点から、DKK2が非荷重およびアンドロゲン欠乏によるサルコペニアと骨粗鬆症に寄与することを初めて報告した。さらに、本研究成果から、DKK2は骨粗鬆症とサルコペニアに共通した病態機序に寄与することが示唆され、骨粗鬆症とサルコペニアの診断に有用な血中マーカーや治療標的となる可能性が考えられた。