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The effects of degenerative products from matrix on syanovial cells and chondrocytes metabolism

基质变性产物对滑膜细胞和软骨细胞代谢的影响

基本信息

批准号：
09470312
负责人：
ISHIGURO Naoki
金额：
$ 9.15万
依托单位：
Nagoya University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
1997
资助国家：
日本
起止时间：
1997 至 1998
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-09470312/
关键词：
Matrix metalloproteinase Proteoglycan Cartilage Type I Collagen Molecular Chaperon 47kDa heat shock protein Rat collagen induced arthritis Chemokine

项目摘要

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

收集了54例OA患者膝关节的滑液样本。对34例膝关节骨性关节炎患者进行放射学和磁共振（MR）成像评估，以分类疾病的分期。TIMP-1的含量与MMP-1和MMP-3的含量直接相关，MMP-1和MMP-3的含量也彼此相关，证实了早期的结果。Δ di-C6 S/Δ di-C4 S比值与MMP-3呈负相关。DELTAdi-C6 S与KS表位相关，并且在较小程度上与846表位相关（后者也与Ddi-C4 S相关）。TIMP-1与846表位相关，TIMP-2与CPII相关，晚期OA患者SF中DELTAdi-C6 S、DELTAdi-C4 S、846表位和CPII的浓度明显降低。软骨基质结构成分含量的减少表明， ...更多信息如前所述，在疾病中。因此，我们研究了TNF-α对大鼠成骨细胞样骨肉瘤细胞（ROS 17/2.8）中NF-κ B活化的影响。电泳迁移率变动分析显示，TNF-α早在15 min就诱导p50-p65异源聚合物NF-κ B的激活，随后持续激活48 h。胞浆中NF-κ B的结合活性在最初的30分钟内下降，然后增加到未刺激的水平。北方印迹分析显示，TNF-α作用6 h后，p50的前体p105 mRNA水平显著增加，而p65 mRNA水平在最初1 h内逐渐增加。抗氧化剂显著减弱了这些mRNA的TNF-α依赖性增加，同时减少了TNF-α对NF-κ B的激活。这些结果表明，TNF-α激活NF-κ B可能在成骨细胞产生细胞因子中起重要作用，导致促进骨吸收和炎症。少