2023 Fiscal Year Final Research Report

A Novel Approach Targeting Metabolic Reprogramming for the Treatment of Destructive Temporomandibular Joint Cartilage Diseases

Research Project

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Project/Area Number	20H03896
Research Category	Grant-in-Aid for Scientific Research (B)
Allocation Type	Single-year Grants
Section	一般
Review Section	Basic Section 57070:Developmental dentistry-related
Research Institution	Osaka University
Principal Investigator	INUBUSHI TOSHIHIRO 大阪大学, 歯学部附属病院, 講師 (30550941)
Co-Investigator(Kenkyū-buntansha)	古郷幹彦大阪大学, 大学院歯学研究科, 名誉教授 (20205371) 黒坂寛大阪大学, 大学院歯学研究科, 准教授 (20509369) 阿部真土大阪大学, 大学院歯学研究科, 講師 (40448105) 佐々木淳一大阪大学, 大学院歯学研究科, 講師 (50530490) 山城隆大阪大学, 大学院歯学研究科, 教授 (70294428) 宇佐美悠大阪大学, 大学院歯学研究科, 講師 (80444579)
Project Period (FY)	2020-04-01 – 2024-03-31
Keywords	ヒアルロン酸 / Tmem2 / 変形性関節症
Outline of Final Research Achievements	In this study, it has been shown that Tmem2 is broadly expressed in knee cartilage, and that its expression increases in the superficial layer of articular cartilage in the early stages of osteoarthritis (OA). It has also been demonstrated that OA progresses significantly in Tmem2 knockout OA model mice. The accumulation of hyaluronic acid (HA) due to the loss of Tmem2 does not act protectively in articular cartilage, but rather may have a destructive effect. The results of this study suggest that the appropriate degradation and synthesis of HA by Tmem2 is important for the maintenance of homeostasis in articular cartilage, and that the disruption of HA regulatory mechanisms is associated with the onset and exacerbation of OA.
Free Research Field	歯科矯正学
Academic Significance and Societal Importance of the Research Achievements	本研究成果より、Tmem2が顎関節軟骨破壊性疾患の発症・進行機序解明ならびに新規治療法開発において新たな分子標的となることが期待でき、大きな意義を有している。また、HAの低分子化は膝関節OA、癌、難聴肺線維症や皮膚炎などの病態とも関わっており、本研究で得られた知見はこれらの疾患の病態解明や治療法開発へも応用可能であり、高い創造性を有しており、その学術的意義は非常に高い。