Objectives. A recent work has reported that the elevated osteopontin (OPN) levels in the articular cartilage and synovial fluid are correlated with the progressive osteoarthritis (OA) joint damage, and OPN has a protective effect against OA by suppressing the expressions of OA-associated genes. The present study examined whether the OPN deficiency was susceptible to OA through the regulation of chondrocyte senescence and apoptosis and the expressions of OA-associated genes. Methods. The mRNA levels of COL2A1 and OPN were compared between human OA chondrocytes and normal chondrocytes. The effects of OPN siRNA on the SA-β-Gal expressions and the percentage of apoptotic chondrocytes were examined by using SA-β-Gal staining and apoptosis assay, and the effects on the expressions of COL2A1 and OA-associated genes (COL10A1, IL-1β, TNF-ɑ, MMP-13, and ADAMTS5) were examined by western blot analysis and quantitative real-time RT-PCR. Furthermore, an in vivo OA model was established to examine the effects of OPN siRNA on the senescence and apoptosis of OA chondrocytes and the expressions of OA-associated genes. Results. The mRNA levels of COL2A1 and OPN were decreased in knee OA chondrocytes in comparison with those in normal chondrocytes. The OPN deficiency enhanced the senescence and apoptosis of OA chondrocytes and increased the expressions of COL10A1, IL-1β, TNF-ɑ, MMP-13, and ADAMTS5 but decreased the expression of COL2A1. Meanwhile, OPN deficiency could result in severe, accelerated OA in vivo, which was also associated with enhanced senescence and apoptosis of chondrocytes and elevated expressions of OA-associated genes. Conclusions. The findings of this study suggest that the OPN deficiency can result in accelerated OA, which is associated with enhanced senescence and apoptosis of OA chondrocytes and the upregulated expressions of OA-associated genes.

中文翻译：

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OPN缺乏会增加与异常软骨细胞衰老和凋亡相关的骨关节炎的严重程度，并上调骨关节炎相关基因的表达

目标。最近的一项工作报道说，关节软骨和滑液中骨桥蛋白（OPN）的升高与进行性骨关节炎（OA）关节损伤相关，并且OPN通过抑制OA相关基因的表达而对OA具有保护作用。本研究通过调节软骨细胞的衰老和凋亡以及与OA相关的基因的表达来检查OPN缺乏是否易受OA的影响。方法。比较了人OA软骨细胞和正常软骨细胞中COL2A1和OPN的mRNA水平。用SA- β检测OPN siRNA对SA- β- Gal表达和凋亡软骨细胞百分比的影响-western印迹分析和定量实时分析了Gal染色和凋亡测定，以及对COL2A1和OA相关基因（COL10A1，IL- 1β，TNF-α，MMP-13和ADAMTS5）表达的影响RT-PCR。此外，建立了体内OA模型以检查OPN siRNA对OA软骨细胞的衰老和凋亡以及OA相关基因表达的影响。结果。与正常软骨细胞相比，膝骨OA软骨细胞中COL2A1和OPN的mRNA水平降低。该OPN缺陷增强OA软骨细胞的衰老和凋亡和增加的COL10A1，的表达IL-1 β，TNF-α，MMP-13和ADAMTS5，但降低了COL2A1的表达。同时，OPN缺乏可能导致体内严重，加速的OA，这还与软骨细胞的衰老和凋亡增强以及OA相关基因的表达升高有关。结论。这项研究的发现表明，OPN缺乏会导致OA加速，这与OA软骨细胞的衰老和凋亡增加以及OA相关基因的表达上调有关。