| Project/Area Number |
16390286
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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 |
膠原病・アレルギー・感染症内科学
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| Research Institution | Tokyo Medical and Dental University |
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Principal Investigator |
HARIGAI Masayoshi Tokyo Medical and Dental University Hospital, Clinical Research Center, Associate Professor, 医学部附属病院, 助教授 (20238207)
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| Co-Investigator(Kenkyū-buntansha) |
MIYASAKA Nobuyuki Tokyo Medical and Dental University, Graduate School Department of Medicine and Rheumatology, Professor, 大学院医歯学総合研究科, 教授 (30157622)
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| Project Period (FY) |
2004 – 2005
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| Project Status |
Completed (Fiscal Year 2005)
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| Budget Amount *help |
¥14,300,000 (Direct Cost: ¥14,300,000)
Fiscal Year 2005: ¥6,900,000 (Direct Cost: ¥6,900,000)
Fiscal Year 2004: ¥7,400,000 (Direct Cost: ¥7,400,000)
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| Keywords | articular chondrocyte / regenerative medicine / proteoglycan / chondrocyte / bone morphogenic protein / 軟骨 / 関節リウマチ / アデノウイルス / 3次元培養 / 遺伝子導入 / 軟骨保護遺伝子 / BMP / ARC軟骨 |
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| Research Abstract |
Background and purpose: Degeneration of articular cartilage tissue is derived from imbalance between anabolic and catabolic factors for articular chondrocytes. We performed this study to obtain insight into efficient chondroprotective methods using recently developed alginate-recovered-chondrocyte tissue and adenoviral gene transfer technique.
Methods : Synthesis and degradation of proteoglycan (PG) were assessed using 35sulfate and alcian blue rapid filtration assay. PG was quantified using dimethylmethylene blue dye binding method. Bone morphogenic protein-7 (BMP-7) and matrix metalloproteinase-3 (MMP-3) were measured using ELISA.
Results : Adenoviral vector (Adv) efficiently transduced target genes into ARC tissue. A significant amount of BMP-7 was secreted by Adv/BMP-7-transduced ARC tissue up to three weeks. Adv/BMP-7 increased synthesis and content of PG of ARC tissue. IL-1□ increased degradation and release of PG as well as production of MMP-3 of ARC tissue. Adv/BMP-7 canceled these anabolic effects of IL-lb on ARC tissue.
Conclusion : Adenoviral gene transfer is an efficient method to express target genes in ARC tissue. Adv/BMP-7 showed significant chondroprotective effects on IL-1b-stimulated ARC tissue. These results suggest that gene-transfer or induction of BMP-7 in affected joints would provide chondroprotection in vivo.
Collaborating foreign investigator : Koichi Masuda, Department of Orthopedics, Rush Medical College
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