Generating novel therapeutic strategies to rejuvenate bone repair capacity

2021 Fiscal Year Final Research Report

• Project/Area Number: 20K18023
• 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 Toyama
• Principal Investigator: Yahara Yasuhito 富山大学, 学術研究部医学系, 助教 (60456390)
• Project Period (FY): 2020-04-01 – 2022-03-31
• Keywords: 破骨細胞 / 造血幹細胞 / 卵黄嚢 / マクロファージ

Outline of Final Research Achievements

Bone repair capacity declines with aging, but the mechanism of this phenomenon is unknown. As a result of this study, we newly discovered the existence of fetal yolk sac-derived osteoclasts that contribute to bone repair. Macrophages generated in the fetal yolk sac migrate to bone during the embryonic period and differentiate into osteoclasts that are responsible for bone resorption. Osteoclasts derived from fetal macrophages resided in postnatal bone for a long-term and were involved in bone homeostasis. Furthermore, once bone injury occurs, they migrate to the local area during the subacute and chronic phases of the repair process and participate in bone remodeling after injury. Fetal-derived osteoclasts may be a factor influencing the transition of bone remodeling capacity throughout life.

Free Research Field

骨代謝、骨免疫学

Academic Significance and Societal Importance of the Research Achievements

本研究の成果として、マクロファージおよび破骨細胞には、造血幹細胞と胎児卵黄嚢を起源とする二種類の細胞集団が存在することを世界に先駆けて発見し報告した。起源の異なる二つの破骨細胞は複雑に細胞融合を繰り返しながら、相互に影響しあうことで、骨の再構築を駆動し、その恒常性維持に関わっていた。新しい破骨細胞分画が発見されたことで、破骨細胞の活性化や機能障害によって発症する疾患の病態解明につながる重要な成果と考えられた。