| Project/Area Number |
13470311
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Orthopaedic surgery
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| Research Institution | Osaka University |
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Principal Investigator |
OCHI Takahiro Osaka University Graduate School of Medicine, Professor, 医学系研究科, 教授 (80112035)
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| Co-Investigator(Kenkyū-buntansha) |
HASHIMOTO Jun Osaka University Graduate School of Medicine,Lecturer, 医学系研究科, 講師 (40237938)
SUGAMOTO Kazuomi Osaka University Graduate School of Medicine,Associate Professor, 医学系研究科, 助教授 (40294061)
冨田 哲也 大阪大学, 医学系研究科, 助手 (30283766)
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| Project Period (FY) |
2001 – 2002
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| Project Status |
Completed (Fiscal Year 2002)
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| Budget Amount *help |
¥13,900,000 (Direct Cost: ¥13,900,000)
Fiscal Year 2002: ¥5,300,000 (Direct Cost: ¥5,300,000)
Fiscal Year 2001: ¥8,600,000 (Direct Cost: ¥8,600,000)
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| Keywords | rheumatoid arthritis / nurse cell / bone marrow / osteochondral destruction / TRAP-positive cell / 慢性関節リウマチ / 骨・軟骨破壊 |
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| Research Abstract |
We have shown the involvement of bone marrow lesion in joint destruction of the partents with rheumatoid arthritis. We found the process of the generation of these TRAP positive multinuclear cells in vitro. Which would be involved in pathogenesis of accelerated bone resorption in juxta-articular bone in RA patients. At first we found that marrow of RA patients have almost the same function with nurse cells which showed pseudoemperiporesis in mouse thymus. These marrow of RA patients have almost the same function with nurse cells which showed pseudoemperiporesis in mouse thymus. These cells. Nurse-like cells. From the synovial tissue and bone marrow of patients with RA support highly activated blood cells through pseudoemperiporesis. CD14(-)periphcral-blood monocytes from healthy individual are supported by co-cultured nurse-like cells from synovial tissues of patients with RA and activated and differentiated into TRAP positive mononuclear cells within 5 weeks of culture. These mononucl
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ear cells then fused and differentiated into multinucleared giant cells after stimulation with IL-3, IL-5, IL-7, and/or granulocyte-macrophage-colony-stimulating factor. These multinucleated giant cells have ability of forming pits on dentin slice which suggests the bone resorbing activity and express the vitronectin receptor. And carbonic anhydrase 11 by immunocytochemistry. These multinucleated giant cells have ability of forming pits on dentin slice which suggests the bone resorbing activity. These TRAP (+) mononuclear and multinucleated cells also expressed MMP-2 (gelatinase-A). MMP-9(gelatinase-B).MMP-12(macrophage metalloelastse) and MMP-14 (MT1-MMP) mPNA in RT-PCR and northern blot analysis. Immunocytochemistry for these MMPs showed that MMP-2 and MMP-9 and MMP-14 were produced by TRAP positive multinucleated cells. TRAP positive mononuclear cells also induced the release of S^<35> from relabeled cartilage discs. These results indicate that TRAP-positive mononuclear cells located in the synovium at the cartilage synovial interface produce MMP-2 and 9 and can play an important role in articular cartilage destruction. TRAP-positive multinucleated cells proliferated in the subchondral bone marrow space. Most of those are osteoclasts. Are closely associated to accelerated bone resorption in RA patients. Both TRAP-positive cells play main roles in joint destruction and supported by abundant fibroblast-like cells in the synovial tissues in joint and bone marrow space. On the other hand. The retardation of growth plate adjacent to affected joint in juvenile rheumatoid arthritis. We also showed that the growth plate was damaged in early stage of arthritis in collagen induced arthritic rats. The destruction of growth plate was not a sequence of the articular destruction but a event independent from articular synovitis in space and accompanied with the increased expression of MMP-3 and VGEF in hypertrohic cartilage cells. These findings also showed the bone marrow lesion involvement in growth plate destruction in arthritis. Less
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