| Project/Area Number |
06670505
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
内科学一般
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| Research Institution | St.Marianna Medical University |
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Principal Investigator |
HIGAKI Megumu St.Marianna Med Univ.Inst.Med.Sci.Associate Prof., 医学部, 助教授 (70156553)
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| Co-Investigator(Kenkyū-buntansha) |
坂根 剛 聖マリアンナ医科大学, 医学部, 教授 (40127519)
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| Project Period (FY) |
1994 – 1995
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| Project Status |
Completed (Fiscal Year 1995)
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| Budget Amount *help |
¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 1995: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 1994: ¥1,200,000 (Direct Cost: ¥1,200,000)
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| Keywords | Vitamin D3 / Rheumatoid arthritis / Synovial cells / cytokine / proliferation / transcription factor / cell cycle / cyclin / 細胞増殖 / コラゲナーゼ |
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| Research Abstract |
Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized with neocvascularization, lymphocytes infiltration and lining cell hyperplasia in inflamed synovial tissues. The hyperproliferated synovial cells called pannus consists of macrophage-like type A synoviocytes and fibroblast-like type B synoviocytes. The type B synoviocytes, which are activated with cytokines such as IL-1 and PDGF produced by type A synoviocytes, proliferate and produce many chemical mediators including cytokines, MMPs, and PGs. Here we have examined the inhibitory effect of vitamin D3 against the activation and proliferation of type B synoviocytes. Vitamin D3, but not dexamethasone, inhibited the proliferation of synoviocytes from RA and osteoarthritis patients dose-dependently. Vitamin D3 inhibited the growth of synoviocytes in G1 phase in cell-cyle analysis using flow cytometry and the inhibition of the expression of cyclin D1 was shown in northern blot analysis. Vitamin D3 also suppressed the production of IL-6 and collagenase, but not TIMP from synoviocytes. Gelatin zymograph also showded the reduction of collagenase acitivity with vitamin D3. And gel-shift assay revealed that vitamin D3 as well as dexamethasone inhibited the nuclear factor AP-1 of IL-1 stimulated synoviocytes.
It is Shown that vitamin D3 inhibited the activation and proliferation of type B synoviocytes and might modulate the pathology of RA.
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