Novel Therapeutic Approach to Rheumatoid Arthritis through Regulation of Autophagy in Synovial Fibroblasts
| Project/Area Number |
18K16134
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 54020:Connective tissue disease and allergy-related
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| Research Institution | Hokkaido University |
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Principal Investigator |
Kato Masaru 北海道大学, 大学病院, 助教 (10755896)
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| Project Period (FY) |
2018-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
Fiscal Year 2019: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| Keywords | 関節リウマチ / 滑膜線維芽細胞 / オートファジー / 関節破壊 / オートファジーレセプター |
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| Outline of Final Research Achievements |
This study has clarified that (1) optineurin, one of the autophagy receptors, is increased on synovial fibroblasts upon stimulation with TNF-alfa, IL-1beta, or IFN-gamma, (2) optineurin negatively regulates RANKL, (3) downregulation of optineurin in synovial fibroblasts suppresses the differentiation of cocultured monocytes into osteoclasts. These results are novel findings in the therapeutic approach to rheumatoid arthritis, particularly in the inhibition of joint destruction, and suggest optineurin as a novel therapeutic target in the treatment of rheumatoid arthritis.
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| Academic Significance and Societal Importance of the Research Achievements |
関節リウマチの治療における最も重要な要素は関節破壊の抑制である。オプチニューリンが滑膜線維芽細胞においてRANKLの発現を負に調節しているという今回の研究成果に加え、滑膜線維芽細胞の発現するRANKLが関節破壊に特に寄与していること（Danks L, et al. Ann Rheum Dis 2016）、オプチニューリンが単球系細胞においても破骨細胞の分化を抑制していること（Obaid R, et al. Cell Rep 2015）が報告されており、これらの知見は関節破壊を抑制する上での新たな治療戦略の基盤となると考えられる。
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Report
(3 results)
Research Products
(6 results)
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[Presentation] Autophagy receptor optineurin in synovial fibroblasts plays a protective role against joint destruction in rheumatoid arthritis2019
Author(s)
Lee W, Kato M, Sugawara E, Kono M, Kudo Y, Kono M, Fujieda Y, Bohgaki T, Amengual O, Oku K, Yasuda S, Atsumi T
Organizer
The 83rd American College of Rheumatology Annual Meeting
Related Report
Int'l Joint Research
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[Presentation] Autophagy promotes citrullination of vimentin and its interaction with major histocompatibility complex class II in synovial fibroblasts2019
Author(s)
Sugawara E, Kato M, Kudo Y, Lee W, Kono M, Fujieda Y, Bohgaki T, Amengual O, Oku K, Yasuda S, Atsumi T
Organizer
The 63rd Annual General Assembly and Scientific Meeting of the Japan College of Rheumatology
Related Report
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[Presentation] The autophagy receptor optineurin negatively regulates RANKL expression in synovial fibroblasts derived from patients with rheumatoid arthritis2019
Author(s)
Lee W, Kato M, Sugawara E, Kono M, Hisada R, Kudo Y, Kono M, Fujieda Y, Bohgaki T, Amengual O, Oku K, Yasuda S, Atsumi T
Organizer
The 63rd Annual General Assembly and Scientific Meeting of the Japan College of Rheumatology
Related Report
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