Regulatory mechanism of mesenchymal stem cell differentiation based on HMGB2 in musculoskeletal fragility

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K18470
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 56020:Orthopedics-related
• Research Institution: University of Miyazaki
• Principal Investigator: Deokcheol Lee 宮崎大学, 医学部, プロジェクト研究員 (60768175)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: HMGB2 / サルコペニア / 骨格筋 / 異所性脂肪 / β-catenin / 酸化ストレス

Outline of Final Research Achievements

Deterioration of muscle quality, such as ectopic fat infiltration, directly reduces muscle strength and causes sarcopenia. Our recent study showed that high-mobility group box 2 (HMGB2) deficiency in mesenchymal stem cells (MCSs) reduces the differentiation potency into adipocytes.
This study showed that β-catenin expression and anti-oxidative stress capacity were also enhanced in MSCs from HMGB2 knockout (KO) mice. Furthermore, muscular volume less decreased, and the expression of adipogenesis-promoting factors and fat infiltration in muscles was less induced in HMGB2 KO mice than in wild-type mice during aging or in a sarcopenia-inducing model. Thus, our findings indicate that HMGB2 induces adipogenesis or fat infiltration into muscles by inhibiting the Wnt/β-catenin pathway and the reaction to anti-oxidative stress.

Free Research Field

整形外科学

Academic Significance and Societal Importance of the Research Achievements

健康寿命の阻害因子である加齢性骨格筋減少症（サルコペニア）は新しい概念であり、その機序の解明が急務である。サルコペニアにおいて、骨格筋内の異所性脂肪が直接的に筋力を低下させるとの知見が近年増えている。Wnt/β-catenin経路や酸化ストレス反応などに作用する、HMGB2の筋内脂肪発生制御機構を明らかにしたことは、サルコペニアのみならず加齢現象の予防・治療法研究に貢献することと考えられる。