Identification of novel mesenchymal cells regulating bone homeostasis

2020 Fiscal Year Final Research Report

• Project/Area Number: 19K18943
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 57010:Oral biological science-related
• Research Institution: The University of Tokyo (2020); Tokyo Medical and Dental University (2019)
• 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): 2019-04-01 – 2021-03-31
• Keywords: 骨免疫 / 骨代謝

Outline of Final Research Achievements

While exploring novel regulators of bone metabolism, we found a protein post-translational modification enzyme Hmtf, which is highly expressed in bone tissue. We have found that Hmtf is an essential factor for the maintenance of skeletal stem cells in the periosteum. We also focused on OPG, a central molecule in the regulation of bone metabolism. We generated OPG-floxed mice and found that OPG is mainly produced by osteoblasts in the bone, intestinal M cells in the intestine, and thymic medullary epithelial cells in the thymus. In addition, we analyzed the differentiation pathway of osteoclasts by using single-cell RNA-seq, and clarified the biological events that take place during the fate determination of osteoclasts.

Free Research Field

骨免疫学

Academic Significance and Societal Importance of the Research Achievements

本研究において我々は、骨を保護するタンパクを産生する細胞の同定と、骨を破壊する細胞が作られる仕組みの解明に成功した。骨の恒常性を制御する細胞の多様性や機能を詳細に解明することは、骨粗鬆症、関節リウマチ、歯周病、がん骨転移といった様々な骨疾患の病態理解や、新しい治療法開発につながると期待される。