Department of Orthopaedics, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha 410008, Hunan, China.
Department of Orthopaedics, Yiyang Central Hospital, 118 North KangFu Road, Yiyang, Hunan 413000, China.
Pain Res Manag. 2020 Oct 22;2020:3428587. doi: 10.1155/2020/3428587. eCollection 2020.
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.
The mRNA levels of COL2A1 and OPN were compared between human OA chondrocytes and normal chondrocytes. The effects of OPN siRNA on the SA--Gal expressions and the percentage of apoptotic chondrocytes were examined by using SA--Gal staining and apoptosis assay, and the effects on the expressions of COL2A1 and OA-associated genes (COL10A1, IL-1, 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.
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-1, 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.
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.
最近的一项研究报道，关节软骨和滑液中骨桥蛋白（OPN）水平的升高与进行性骨关节炎（OA）关节损伤相关，OPN 通过抑制 OA 相关基因的表达对 OA 具有保护作用。本研究通过检测 OPN 缺乏是否通过调节软骨细胞衰老和凋亡以及 OA 相关基因的表达而导致 OA，以检验上述观点。
比较了人 OA 软骨细胞和正常软骨细胞中 COL2A1 和 OPN 的 mRNA 水平。通过 SA-β-gal 染色和凋亡检测，观察 OPN siRNA 对 SA-β-gal 表达和凋亡软骨细胞百分比的影响，通过 Western blot 分析和定量实时 RT-PCR 检测 OPN siRNA 对 COL2A1 和 OA 相关基因（COL10A1、IL-1、TNF-ɑ、MMP-13 和 ADAMTS5）表达的影响。此外，建立体内 OA 模型，以检测 OPN siRNA 对 OA 软骨细胞衰老和凋亡以及 OA 相关基因表达的影响。
与正常软骨细胞相比，膝部 OA 软骨细胞中 COL2A1 和 OPN 的 mRNA 水平降低。OPN 缺乏增强了 OA 软骨细胞的衰老和凋亡，增加了 COL10A1、IL-1、TNF-ɑ、MMP-13 和 ADAMTS5 的表达，但降低了 COL2A1 的表达。同时，OPN 缺乏可导致体内 OA 加重且加速，这与软骨细胞衰老和凋亡增加以及 OA 相关基因表达上调有关。
本研究结果表明，OPN 缺乏可导致 OA 加重，其与 OA 软骨细胞衰老和凋亡增加以及 OA 相关基因表达上调有关。
Zotero 插件
