Reduced expression and proteolytic susceptibility of lubricin/superficial zone protein may explain early elevation in the coefficient of friction in the joints of rats with antigen-induced arthritis
Reduced expression and proteolytic susceptibility of lubricin/superficial zone protein may explain early elevation in the coefficient of friction in the joints of rats with antigen-induced arthritis
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DOI：
10.1002/art.22321
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发表时间：
2007-01-01
影响因子：
--
通讯作者：
Chichester, Clinton O.
中科院分区：
文献类型：
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作者：
Elsaid, Khaled A.;Jay, Gregory D.;Chichester, Clinton O.
目标。目的探讨关节炎的发生发展对润滑剂完整性和功能的影响，以及润滑剂与关节软骨损伤的关系。用甲基化牛血清白蛋白和弗氏完全佐剂诱导右膝关节关节炎。用改进的Stanton摆结构在体外进行了全关节摩擦测量，并测定了摩擦系数(V)。用定量聚合酶链式反应检测对照组和患侧关节滑膜组织中润滑素、组织蛋白酶B和白细胞介素1β(IL-1β)的信使核糖核酸(MRNA)水平。用抗润滑素的单抗对软骨进行润滑素染色。右关节切除组的MU值显著高于左关节切除组(P<；0.001)。在关节炎诱导后第4天和第7天，右侧关节滑膜组织中润滑素基因表达水平显著低于左侧关节(P<；0.001)，而组织蛋白酶B和IL-1β在第4、7和14天的表达水平显著高于左侧关节(P<；0.001)。与左侧关节相比，右侧关节软骨中的润滑素染色较少。关节炎关节的摩擦系数增加的同时，上调的组织蛋白酶B和其他蛋白酶促进了蛋白降解，滑膜成纤维细胞和浅区软骨细胞合成的润滑素减少。关节润滑性丧失是炎症性关节病的早期事件。恢复软骨保护和防止潜在的磨损引起的软骨退化可能需要在滑液中补充润滑剂。
Objective. To investigate the effect of arthritis development and progression on the integrity and function of lubricin and the relationship of lubricin to cartilage damage in a rat antigen-induced arthritis model.Methods. Arthritis was induced in the right knee joints, using methylated bovine serum albumin and Freund's complete adjuvant. Whole joint friction measurements were performed ex vivo with a modified Stanton pendulum configuration, and coefficients of friction (V) were determined. Levels of messenger RNA (mRNA) for lubricin, cathepsin B, and interleukin-1 beta (IL-1 beta) in synovial tissue from control and affected joints were determined by quantitative polymerase chain reaction. Lubricin staining in cartilage was performed using a lubricin-specific monoclonal antibody.Results. The mu values in excised right joints following arthritis induction were significantly (P < 0.001) higher than those in excised left joints. Lubricin mRNA expression levels in synovial tissue on days 4 and 7 after arthritis induction were significantly (P < 0.001) lower in the right joints compared with the left joints, whereas levels of cathepsin B and IL-1 beta mRNA expression on days 4, 7, and 14 were significantly (P < 0.001) higher in the right joints than the left joints. Lubricin staining was diminished in cartilage from the right joints compared with the left joints.Conclusion. Elevated coefficients of friction in arthritic joints occur concurrently with enhanced proteolytic degradation by up-regulated cathepsin B and other proteases, as well as decreased lubricin synthesis by synovial fibroblasts and superficial zone chondrocytes. Loss of joint lubrication is an early event in inflammatory arthropathy. Restoring chondroprotection and preventing potential wear-induced cartilage degradation may require lubricin supplementation in synovial fluid.