2021 Fiscal Year Final Research Report

Analysis fo osteoclast-regulated bone marrow aging and its application to rejuvenation of hematopoietic function

Research Project

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Project/Area Number	19K22727
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	Toshihide Mizoguchi 東京歯科大学, 歯学部, 准教授 (90329475)
Co-Investigator(Kenkyū-buntansha)	東俊文東京歯科大学, 歯学部, 教授 (00222612) 荒井敦松本歯科大学, 歯学部, 准教授 (00532772)
Project Period (FY)	2019-06-28 – 2022-03-31
Keywords	破骨細胞 / 脂肪細胞 / 副甲状腺ホルモン / 骨芽細胞 / 骨髄 / 骨格幹細胞
Outline of Final Research Achievements	The hematopoietic function of the bone marrow environment is attenuated with aging. One of the causes of this defect is induction of adipocytogenesis in the bone marrow tissue. Adipocytes are differentiated from skeletal stem cells (SSCs). It is suggested that adipocytic differentiation of SSCs is accelerated with aging; however, the mechanism is unclear. In a previous study, we identified SSCs as leptin receptor (LepR)-positive cells. In this study, we used Cre/loxP-based lineage tracing analysis to understand the regulatory mechanism of adipocytogenesis from SSCs. We revealed that: (1) adipocytes that increased in ovariectomized (OVX) osteoporotic mice were differentiated from LepR+SSCs and (2) administration of Teriparatide (PTH (1-34)), a medicine for osteoporosis to OVX mice, shifted the direction of lineage differentiation of LepR+ SSCs from adipocytes toward osteoblasts.
Free Research Field	骨代謝
Academic Significance and Societal Importance of the Research Achievements	学術的意義：本研究により、骨粗鬆症を呈した骨組織ではLepR-creで標識したSSCsの脂肪細胞分化が亢進することが示された。また、PTH(1-34)は骨粗鬆症状態の骨髄環境下においてもSSCsの分化の方向性を骨芽細胞側にシフトすることが分かった。したがって、本研究成果は、SSCsの分化調節機構の解明に繋がる有意義な内容である。社会的意義：超高齢化社会を迎える本邦において、「健康寿命」の延長は最重要課題である。健康寿命を短縮する大きな要因として、骨密度減少による足の骨折が挙げられ、これにより寝たきりになる可能性が高まる。骨量の維持に繋がる本研究成果は、健康寿命の延伸に繋がる重要な内容である。