Pathogenesis of bone destruction in rheumatoid arthritis and its relation to ADAM-17 and development of novel drugs

2020 Fiscal Year Final Research Report

• Project/Area Number: 19K17896
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 54020:Connective tissue disease and allergy-related
• Research Institution: Showa University
• Principal Investigator: Furuya Hidekazu 昭和大学, 医学部, 助教 (80748864)
• Project Period (FY): 2019-04-01 – 2021-03-31
• Keywords: ADAM-17 / 関節リウマチ / 骨芽細胞

Outline of Final Research Achievements

ADAM-17 was shown to be highly expressed in bone tissue and osteoblasts of rheumatoid arthritis. The expression of ADAM-17 in RA osteoblasts (RA-HOB) was further enhanced under inflammatory conditions by stimulation with TNF-α. In addition, the intracellular signaling of ADAM-17 in RA-HOB was shown to be mediated by NFκ-B. Regarding the function of ADAM-17 in RA-HOB, it was demonstrated that suppression of ADAM-17 inhibited osteoblast cell proliferation and migration. These results suggest that ADAM-17 is highly expressed in osteoblasts of rheumatoid arthritis and may promote migration and proliferation of osteoblasts.

Free Research Field

関節リウマチの病態の解明

Academic Significance and Societal Importance of the Research Achievements

これまで関節リウマチの炎症病態におけるADAM-17の関与に関しては報告が散見されていたが、骨代謝との関連に関しては報告がない。今回の研究から関節リウマチの骨芽細胞にはADAM-17が高発現しており、骨芽細胞の遊走と増殖を促進するという結果が得られ、ADAM-17が関節リウマチにおける骨代謝に関与するという初めての報告となる。今後ADAM-17が関節リウマチの治療の標的となる可能性もあり、治療学の発展に寄与するものと考えている。