Application to the rheumatoid arthritis treatment of a small molecule compound inhibiting differentiation and a function of osteoclasts
Project/Area Number |
18K16161
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Research Category |
Grant-in-Aid for Early-Career Scientists
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Allocation Type | Multi-year Fund |
Review Section |
Basic Section 54020:Connective tissue disease and allergy-related
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Research Institution | Jikei University School of Medicine |
Principal Investigator |
MAEDA KAZUHIRO 東京慈恵会医科大学, 医学部, 講師 (50548849)
|
Project Period (FY) |
2018-04-01 – 2022-03-31
|
Project Status |
Completed (Fiscal Year 2021)
|
Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2020: ¥520,000 (Direct Cost: ¥400,000、Indirect Cost: ¥120,000)
Fiscal Year 2019: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
|
Keywords | 関節リウマチ / 炎症性サイトカイン / 破骨細胞 / 骨吸収 / Wnt |
Outline of Final Research Achievements |
The secretory glycoprotein Wnt5a promotes RANKL-induced osteoclast differentiation and function via the receptor-type tyrosine kinase Ror2. Wnt5a is overexpressed in the rheumatoid arthritis (RA) synovium. For the purpose of suppressing bone destruction by RA, we conducted an administration experiment of a low molecular weight compound that inhibits the kinase downstream of Ror2 to the RA model mice. As a result, it was clarified that the low molecular weight compound administration group significantly suppressed the joint destruction as compared with the control compound administration group. It was suggested that this pathway may be a molecular target for suppressing the joint destruction of RA.
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Academic Significance and Societal Importance of the Research Achievements |
本経路は炎症性サイトカインやmatrix metalloproteinase(MMP)の産生にも関与するとの報告が散見される。現在、RAの治療は生物学的製剤が用いられているが、そのほとんどは炎症性サイトカインを標的としたものである。骨代謝、炎症性サイトカイン産生および MMP産生の3つに共通した経路を分子標的とすることは、骨破壊、炎症による痛みおよび軟骨破壊のそれぞれの病態を改善させるのに有用と考える。
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Report
(5 results)
Research Products
(17 results)
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[Journal Article] Ex Vivo Gene Therapy Treats Bone Complications of Mucopolysaccharidosis Type II Mouse Models through Bone Remodeling Reactivation.2020
Author(s)
Wada M, Shimada Y, Iizuka S, Ishii N, Hiraki H, Tachibana T, Maeda K, Saito M, Arakawa S, Ishimoto T, Nakano T, Ida H, Ohashi T, Kobayashi H.
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Journal Title
Mol Ther Methods Clin Dev.
Volume: 19
Pages: 261-274
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] A case of carpal tunnel syndrome caused by giant gouty tophi: The usefulness of DECT for the diagnosis, preoperative planning, and postoperative evaluation of atypical cases.2019
Author(s)
Kazuhiro Maeda, Hiroyuki Chino, Tadashi Tokashiki, Jun Udaka, Yuya Okutsu, Mitsuhito Yukawa, Makoto Mitsuhashi, Naoya Inagaki, Hirofumi Osumi, Yuji Nagamine, Tetsuro Nishizawa, Tomohiro Kayama, Takeshi Fukuda, Kunihiko Fukuda, Hiroya Ojiri, Keishi Marumo
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Journal Title
Mod Rheumatol Case Rep.
Volume: 3
Issue: 2
Pages: 165-171
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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