Analysis of osteoclast progenitors using a novel high-sensitivity detection method for RANK-expressing cells

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K19615
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Review Section: Medium-sized Section 57:Oral science and related fields
• Research Institution: Tokyo Dental College
• Principal Investigator: Mizoguchi Toshihide 東京歯科大学, 歯学部, 教授 (90329475)
• Project Period (FY): 2021-07-09 – 2024-03-31
• Keywords: 破骨細胞 / 破骨細胞前駆細胞 / GST-RANKL / RANK / M-CSF / CSF-1R

Outline of Final Research Achievements

The in vivo dynamics of osteoclast precursors are not well understood. Osteoclast precursors express receptor of RANKL (RANK). We tried to identify osteoclast precursors in vivo using GST-RANKL. The following findings were revealed in our study. (1) RANK-positive cells in bone marrow and bloodstream were detected as macrophage lineages and B cells. (2) Osteoclast differentiation was more detected in B220-RANK-CSF-1R+ cells in the bone marrow, and B220-RANK+CSF-1R+ cells in the bloodstream. (3) The clusters found in the Nes-GFP-positive LepR-creER-Tom-positive bone marrow mesenchymal stromal cells included clusters expressing RANKL and M-CSF at high levels.

Free Research Field

骨代謝

Academic Significance and Societal Importance of the Research Achievements

破骨細胞前駆細胞の生体内における動態は良くわかっていない。本研究は、破骨前駆細胞の同定を目的としたものであり、破骨細胞前駆細胞の維持および分化調節を基盤とした骨代謝調節機構の解明に繋がることが期待できる。また、破骨細胞は、造血幹細胞からマクロファージ系の細胞を経由して分化するが、その生体における分化機序は不明である。したがって、本研究の推進は、血液学および免疫学分野にも有用な知見をもたらす可能性を包含する。