Roles of Bone Morphogenetic Protein 2 in postnatal meniscus homeostasis

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K09056
• 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: Koga Hideyuki 東京医科歯科大学, 大学院医歯学総合研究科, 教授 (30594080)
• Co-Investigator(Kenkyū-buntansha): 辻 邦和 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 (20323694) ; 関矢 一郎 東京医科歯科大学, 統合研究機構, 教授 (10345291) ; 宗田 大 東京医科歯科大学, 大学院医歯学総合研究科, 非常勤講師 (50190864)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: 半月板 / 骨形成因子 / BMP2 / BMP4 / BMP7

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) and analyzed age related knee joint phenotypes. 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 (not published). In this study we focused on the analyses of meniscus formation in the absence of Bmp2 and showed that chondrogenic differentiation of the cells reside in the meniscus primordium was strictly inhibited after birth.

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。