Analysis of skeletal muscle homeostasis and muscle degeneration

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K09636
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 56020:Orthopedics-related
• Research Institution: National Defense Medical College
• Principal Investigator: Horiuchi Keisuke 防衛医科大学校(医学教育部医学科進学課程及び専門課程、動物実験施設、共同利用研究施設、病院並びに防衛, 整形外科学, 准教授 (30327564)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: 骨格筋 / 骨格筋脂肪変性 / 筋萎縮 / 筋衛星細胞 / 未分化間葉系細胞

Outline of Final Research Achievements

Muscle fatty degeneration is a relatively common disorder characterized by the infiltration or replacement of muscle fibers with fat tissue in skeletal muscle. This condition is often found in patients with skeletal muscle denervation and myopathy. Clinically, fatty degeneration is considered an irreversible event, and it profoundly compromises the elasticity and tensile strength of skeletal muscle. Currently, there is no effective treatment to prevent or abate the progress of this condition. In this research project, we found that retinoic acid receptor signaling is critically involved in the development of fatty degeneration and that fatty degeneration can be suppressed by inhibiting this signaling. Additionally, by using aged mice as a model, we also found that aging renders skeletal muscle susceptible to fatty degeneration after muscle injury. These findings may serve as a basis for establishing a treatment and prophylaxis for muscle degenerative conditions.

Free Research Field

整形外科学

Academic Significance and Societal Importance of the Research Achievements

加齢に伴う運動器の変性疾患として，従来，変形性関節症および骨粗鬆症が主な研究対象であったが，フレイルという疾患概念において骨格筋の重要性は論を俟たない．骨格筋は様々な原因で萎縮，変性を生じ，運動機能を著しく損なう．これらの病態は，高齢者の転倒・転落の一因となることから，臨床的にもその対応は重要である．しかしながら，その対応は物理療法や栄養指導にとどまっており，有効な治療法，予防法が確立されていない．今回の研究結果は，骨格筋の脂肪変性のメカニズムの一端を明らかにし，さらにその予防法までを示唆する内容であり，基礎的な側面だけでなく，臨床的にも重要な知見であると考える．