Elucidation of osteoarthritis defense system based on glucose metabolism in chondrocytes.

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K18756
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 57070:Developmental dentistry-related
• Research Institution: Okayama University
• Principal Investigator: Mizukawa Tomomi 岡山大学, 歯学部, 博士研究員 (60868412)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: TMJ-OA / CCN3 / 糖代謝 / 転写因子 / エンハンサー領域 / 軟骨細胞 / 解糖阻害

Outline of Final Research Achievements

Osteoarthritis (OA) that is observed also in the temporomandibular joints is a chronic disorder harming the quality of life. Impaired glycolysis, which is suggested to be involved in OA development, induces cellular communication factor (CCN) 3 that contributes to the growth regulation and maturation of chondrocytes. In this study, it was clarified that the CCN3 induction by starvation/impaired glycolysis was mediated by regulatory factor binding to the X-box (RFX)1 via a transcription enhancer located near the CCN3 promoter. Moreover, CCN3 produced in this way was found to support the survival of chondrocytes. These findings provide a scientific basis for the development of novel therapeutic approach against OA via the regulation of CCN3 production in cartilage.

Free Research Field

口腔生化学

Academic Significance and Societal Importance of the Research Achievements

本研究による「CCN3遺伝子の転写制御メカニズムの一端が解明された」成果は、新たなTMJ-OA治療法の創造への足場の一つとなる可能性がある。現在のTMJ-OA治療は、夜間のメカニカルストレスを軽減するスプリント装着など、いわば口腔理学療法による予防にとどまる。軟骨破壊に対する再生療法が確立していないのは、整形外科領域のOAと同様だが、その代わりを務める人工物置換術もTMJ-OAでは困難で実施されていない。このような条件下で、TMJ-OA治療に福音をもたらす可能性のある本研究の創造性は鮮明である。