| Project/Area Number |
09470312
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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 | Nagoya University |
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Principal Investigator |
ISHIGURO Naoki School of Medicine, Nagoya University, Assistant Professor, 医学部, 講師 (20212871)
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| Co-Investigator(Kenkyū-buntansha) |
SENOO Hisao Research Institute of Enviromental Medicine, Professor, 環境医学研究所, 教授 (40135380)
ITO Takayasu School of Medicine, Staff, 医学部, 医員
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| Project Period (FY) |
1997 – 1998
|
| Project Status |
Completed (Fiscal Year 1998)
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| Budget Amount *help |
¥14,300,000 (Direct Cost: ¥14,300,000)
Fiscal Year 1998: ¥2,500,000 (Direct Cost: ¥2,500,000)
Fiscal Year 1997: ¥11,800,000 (Direct Cost: ¥11,800,000)
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| Keywords | Matrix metalloproteinase / Proteoglycan / Cartilage / Type I Collagen / Molecular Chaperon / 47kDa heat shock protein / Rat collagen induced arthritis / Chemokine |
|---|
| Research Abstract |
Synovial fluid samples from the knees of 54 patients with OA were collected. Radiographic and magnetic resonance (MR) imaging evaluations were performed on 34 of the OA patientsi knees to classify the stage of the disease. The content of TIMP-1 was directly correlated with those of MMP-1 and -3, which were also correlated with each other, confirming earlier results. There was an inverse correlation between the ratio DELTAdi-C6S/deltadi-C4S and MMP-3. DELTAdi-C6S was correlated with the KS epitope, and to a lesser degree with the 846 epitope (latter also with Ddi-C4S). TIMP-1 correlated with the 846 epitope, TIMP-2 correlated with the CPII.There were significantly lower concentrations of DELTAdi-C6S, DELTAdi-C4S, the 846 epitope and CPII in SF in late stage OA.The production of TIMPs appears to be individually linked to the synthesis of specific cartilage molecules. The reduction in content of cartilage matrix structural components suggest that there is a measurable loss of cartilage la
… More
te in the disease as suggested previously. We thus examined the effect of TNF-alpha on the activation of NF-kappaB in rat osteoblast-like osteosarcoma cells (ROS17/2.8) . Electrophoretic mobility shift assay revealed that the activation of the p5O-p65 heteroclimer NF-kappaB was induced by TNF-alpha as early as 15 mm followed by a persistent activation for 48 h. The binding activity of NF-kappaB in cytosol decreased during the initial 30 min and then increased to the unstimulated level. Northern blot analysis revealed a marked increase in the mRNA levels of p105, a precursor of p50, 6 h after TNF-alpha and a gradual increase in p65 mRNA levels during the initial 1 h. An antioxidant significantly attenuated the TNF-alpha-dependent increase in these mRNAs, and simultaneously reduced the activation of NF-kappaB by TNF-alpha. These results suggest that the activation of NF-kappaB by TNF-alpha may play an important role in the production of cytokines from osteoblasts, leading to the promotion of bone resorption and inflammation. Less
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