A novel therapeutic strategy for the temporomandibular joint osteoarthritis focusing on the osteoclast induction mechanism of temporomandibular joint synovial cells

2022 Fiscal Year Final Research Report

• Project/Area Number: 19K19277
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 57070:Developmental dentistry-related
• Research Institution: Iwate Medical University
• Principal Investigator: Yokota Seiji 岩手医科大学, 歯学部, 講師 (50802401)
• Project Period (FY): 2019-04-01 – 2023-03-31
• Keywords: 変形性顎関節症 / P2Y受容体 / 細胞外ヌクレオチド / ADP / 顎関節由来線維芽細胞様滑膜細胞

Outline of Final Research Achievements

Reverse transcription-quantitative polymerase chain reaction analysis revealed that the P2Y1, P2Y12, and P2Y13 purinergic receptor agonist adenosine 5';-diphosphate (ADP) significantly induces monocyte chemotactic protein 1 (MCP-1)/ C-C motif chemokine ligand 2 (CCL2) expression in the FLS1 synovial cell line. In contrast, the uracil nucleotide UTP, which is a P2Y2 and P2Y4 agonist, has no significant effect on MCP-1/CCL2 production in FLS1 cells. In addition, the P2Y13 antagonist MRS 2211 considerably decreases the expression of ADP-induced MCP-1/CCL2, whereas ADP stimulation enhances extracellular signal-regulated kinase (ERK) phosphorylation. Moreover, it was found that the mitogen-activated protein kinase/ERK kinase (MEK) inhibitor U0126 reduces ADP-induced MCP-1/CCL2 expression.

Free Research Field

生化学

Academic Significance and Societal Importance of the Research Achievements

細胞外ヌクレオチドの一種であるADPはMEK/ERK依存的にP2Y13受容体を介してFLS細胞におけるMCP-1/CCL2のmRNAレベルでの発現量を促進しその結果、顎関節周囲における炎症性細胞浸潤を引き起こすことが示唆された。以上の結果より、本研究は顎関節周囲炎の発症に関する分子メカニズムの部分的な解明に貢献し、TMJ-OAにおけるADP誘導性プリン作動性シグナル伝達経路を介する根本的な治療方法の確立に役立つと考えられる。