| Project/Area Number |
14370472
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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 | Kyoto Prefectural University of Medicine |
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Principal Investigator |
HORII Motoyuki Kyoto Prefectural University of Medicine, Graduate School of Medical Science, Assistant, 医学研究科, 講師 (40219209)
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| Co-Investigator(Kenkyū-buntansha) |
KUBO Toshikazu Kyoto Prefectural University of Medicine, Graduate School of Medical Science, Professor, 医学研究科, 教授 (20178031)
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| Project Period (FY) |
2002 – 2003
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| Project Status |
Completed (Fiscal Year 2003)
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| Budget Amount *help |
¥13,400,000 (Direct Cost: ¥13,400,000)
Fiscal Year 2003: ¥5,800,000 (Direct Cost: ¥5,800,000)
Fiscal Year 2002: ¥7,600,000 (Direct Cost: ¥7,600,000)
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| Keywords | Frzb / Wnt / chondrogenesis / apoptosis / HSP 70 / chondrocyte / osteoarthritis / rheumatoid arthritis / HSP 70 / 炎症性サイトカイン / 関節軟骨 / アデノウイルスベクター / 遺伝子治療 / 分化制御 / 再生医療 |
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| Research Abstract |
The aim of this study is to investigate the therapeutic effect of Frzb on joint diseases and the mechanism of chondrocyte differentiation and apoptosis in their pathogenesis. Firstly, to elucidate the mechanism of chondrocyte apoptosis in osteoarthritis (OA), we examined the function of heat shock protein 70 (FISP 70), which was known to play a pivotal role in OA pathogenesis. HSP 70 was genetically transduced into chondrocytes by means of the adenovirus vector, and the treatment prohibited NO-or staurosporine-induced apoptosis. These findings help elucidate part of the pathogenesis of OA. Secondly, to demonstrate the therapeutic effect of Frzb on joint diseases, we investigate the influence of overexpressed Frzb on the cytokine expression by syonovial fibroblasts of rheumatoid arthritis (RA) and osteoblasts from subchondral bone of OA. Frzb was overexpressed into each primary cells by means of lipofection method. Total RNA was extracted and analyzed by RT-PCR method for IL-1β, IL-6,IL-8 and TNF-αmRNA expression. In osteoblasts from subchondral bone of OA, endogenous Frzb expression was detectable and the expression of inflammatory cytokines decreased after Frzb overexpression. In syonovial fibroblasts of RA, remarkable change of cytokine expression was not observed. These findings suggest that aberrant differentiation of subchondral bone can be involved in the pathogenesis of OA and Frzb can be therapeutic candidate gene of OA. Further research is necessary to find the relationship between Frzb and HSP 70 from the aspect of chondrocyte apoptosis and clarify in vivo therapeutic effect of Frzb on experimental OA in the rabbit knee.
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