Development of a novel therapeutic agent for TMJ disorder focusing on 8-nitro-cGMP

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K19246
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 57060:Surgical dentistry-related
• Research Institution: Tokyo Medical University
• Principal Investigator: Kotaro Kaneko 東京医科大学, 医学部, 助教 (50826964)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: 8-ニトロ-CGMP / 変形性顎関節症 / 破骨細胞 / 骨芽細胞

Outline of Final Research Achievements

Osteoarthritis of the TMJ is often difficult to treat. The effects of nitric oxide (NO) and inflammatory cytokines have been reported as the etiology of osteoarthritis of the TMJ. In this study, we analyzed the production and function of 8-nitro-cGMP, which was found to be a downstream signaling molecule of NO, in osteoclasts and osteoblasts to clarify its role in TMJ osteoarthritis. Osteoclasts and osteoblasts produced 8-nitro-cGMP. Endogenous 8-nitro-cGMP suppressed osteoclast differentiation and osteoblast calcification. These results indicate that 8-nitro-cGMP is involved in the etiology of TMJ osteoarthritis.

Free Research Field

口腔外科

Academic Significance and Societal Importance of the Research Achievements

8-ニトロ-cGMPが骨吸収を促進し、骨形成を抑制することが示唆された。生体内での8-nitro-cGMPの生成経路、シグナル伝達様式および不活性化経路は、すでに明らかになっている。これらの結果から変形性顎関節症のみならず、他部位の変形性関節症や骨粗鬆症など骨量が減少する疾患に8-ニトロ-cGMPが関与している可能性が明らかになった。この研究を続けることにより、それらの疾患に関しての病態改善にもつながることになると思われる。