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

收集54例OA患者膝关节滑液标本。对34例膝关节骨性关节炎患者进行x线和磁共振（MR）成像评估，对疾病分期进行分类。TIMP-1的含量与MMP-1和-3的含量直接相关，两者之间也存在相关性，证实了之前的结果。δ δ - c6s / δ δ - c4s比值与MMP-3呈负相关。DELTAdi-C6S与KS表位相关，与846表位相关程度较低（后者也与Ddi-C4S相关）。TIMP-1与846表位相关，TIMP-2与CPII相关。OA晚期SF中DELTAdi-C6S、DELTAdi-C4S、846表位和CPII的浓度明显降低。timp的产生似乎与特定软骨分子的合成单独相关。软骨基质结构成分含量的减少表明软骨组织有可测量的损失，如前所述。因此，我们研究了tnf - α对大鼠成骨样骨肉瘤细胞NF-kappaB活化的影响（ROS17/2.8）。电泳迁移率转移实验表明，tnf - α可诱导p50 -p65异气候因子NF-kappaB在15 mm内激活，随后持续激活48 h。NF-kappaB在细胞质中的结合活性在最初的30 min内下降，然后上升到未刺激的水平。Northern blot分析显示，p105 （p50的前体）mRNA水平在tnf - α作用后6小时显著升高，p65 mRNA水平在最初的1小时内逐渐升高。抗氧化剂显著减弱了这些mRNA的tnf - α依赖性增加，同时降低了tnf - α对NF-kappaB的激活。这些结果表明，tnf - α激活NF-kappaB可能在成骨细胞产生细胞因子中发挥重要作用，从而促进骨吸收和炎症。少

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