2023 Fiscal Year Final Research Report

Physiological roles of BMP2 in meniscus homeostasis

Research Project

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Project/Area Number	21K09196
Research Category	Grant-in-Aid for Scientific Research (C)
Allocation Type	Multi-year Fund
Section	一般
Review Section	Basic Section 56020:Orthopedics-related
Research Institution	Tokyo Medical and Dental University
Principal Investigator	Tsuji Kunikazu 東京医科歯科大学, 大学院医歯学総合研究科, 特任教授 (20323694)
Co-Investigator(Kenkyū-buntansha)	古賀英之東京医科歯科大学, 大学院医歯学総合研究科, 教授 (30594080) 宮武和正東京医科歯科大学, 大学院医歯学総合研究科, 講師 (00777435) 片桐洋樹東京医科歯科大学, 医学部附属病院, 非常勤講師 (50795028) 中川裕介東京医科歯科大学, 大学院医歯学総合研究科, 寄附講座准教授 (60822666) 中村智祐東京医科歯科大学, 大学院医歯学総合研究科, 准教授 (90725201) 関矢一郎東京医科歯科大学, 統合研究機構, 教授 (10345291)
Project Period (FY)	2021-04-01 – 2024-03-31
Keywords	BMP / TGFb / 半月板 / 関節軟骨
Outline of Final Research Achievements	To elucidate the physiological roles of Bmp2, Bmp4, and Bmp7 in postnatal joint homeostasis, we have created limb specific Bmp conditional knockout mice (Bmp2c/c;Prx1::cre, Bmp4c/c;Prx1::cre, Bmp7c/c;Prx1::cre). We have reported that conditional null mutation of Bmp2 results in the malformation of meniscus and down regulation of type II collagen expression in the superficial region of articular cartilage within 2 weeks after birth. We also reported that conditional null mutation of Bmp7 results in the reduction of proteoglycan contents in articular cartilage after 8 weeks of age. In contrast, we observed subtle morphological changes in articular cartilage and meniscus in the absence of Bmp4. In this study, to further analyze the physiological roles of BMP2 during the knee joint development and in the postnatal homeostasis, we analyzed the spatiotemporal expressions of BMP molecules in the knee joint. We also analyzed the target molecules regulated by BMPs in chondrocytes.
Free Research Field	整形外科学
Academic Significance and Societal Importance of the Research Achievements	半月板は関節機能の維持に必須の組織であるにも関わらず、その発生並びに恒常性の分子機序はほとんど解析されていない。近年では、半月板機能の低下が変形性膝関節症の発症並びに増悪に深く関与していることが報告されている。本研究の成果は、半月板機能の維持に必要な分子機序の解明につながることが期待される。