Novel mechanisms governing the development, maintenance, and destruction of the bony skeleton

2023 Fiscal Year Final Research Report

• Project/Area Number: 21H03104
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 57010:Oral biological science-related
• Research Institution: The University of Tokyo
• Principal Investigator: Tsukasaki Masayuki 東京大学, 大学院医学系研究科(医学部), 特任助教 (20829527)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: 骨免疫学 / 骨代謝学

Outline of Final Research Achievements

Bone functions as a locomotor organ and a mineral reservoir as well as a primary lymphoid organ where hematopoietic stem cells are maintained. Bone homeostasis is maintained by the balance between bone resorption and formation, and disruption of this balance is involved in the pathogenesis of various bone diseases. In this project, we identified novel functions of skeletal stem cells (Tsukasaki, Nature Com 2022), unveiled the molecular mechanisms of osteoclastogenesis (Tsukasaki, Nature Metab 2020), and clarified the cell type- and context- dependent machinery underlying RANKL regulation in osteoclast-supporting cells (Yan, Nature Immunol 2022, Yan, Bone Res 2023, Ando, IJOS 2024). These studies have uncovered the regulatory mechanisms underlying bone homeostasis at unprecedented resolution and shed light on the complex intercellular interactions in bone health and diseases.

Free Research Field

骨免疫学

Academic Significance and Societal Importance of the Research Achievements

本研究により、骨膜の幹細胞が骨成長に寄与することが明らかとなり、骨膜が低身長症を含む様々な骨疾患の治療標的となりうる可能性が示唆された。さらに、破骨細胞分化経路の1細胞レベルでの解明、破骨細胞の新規制御因子の同定、破骨細胞支持細胞におけるRANKL発現機構の解明により、破骨細胞が関与するあらゆる骨吸収性疾患（骨粗鬆症、歯周病、関節リウマチなど）に対する新たな予防・治療法開発へ向けた基盤が構築された。