Shi Shiping, Man Zhentao, Sun Shui
Department of Joint Surgery, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong 250021, P.R. China.
Department of Joint Surgery, Dongying People's Hospital, Dongying, Shandong 257100, P.R. China.
Exp Ther Med. 2022 Jun 17;24(2):526. doi: 10.3892/etm.2022.11453. eCollection 2022 Aug.
Osteoarthritis (OA) is a chronic condition caused by cartilage degradation, and there are currently no effective methods for preventing the progression of this disease; gene therapy is a relatively novel method for treating arthritis. Decreased collagen type II (Col2) expression within the cartilage matrix is an important factor for the development of OA, and Wnt3a serves a significant role in cartilage homeostasis. The present study assessed whether Wnt3a knockdown promoted Col2 expression in chondrocytes. Lentivirus-introduced small interfering RNA was used to knock down the expression of Wnt3a in primary rat chondrocytes, and then IL-1β treatment was used to establish an OA chondrocyte model. The expression of target genes (Wnt3a, Col2, MMP-13 and β-catenin) was analyzed using reverse transcription-quantitative PCR, western blotting and immunocytochemistry. There was significantly less MMP-13 and β-catenin expression in the Wnt3a knockdown cells compared with the other controls. Col2 expression was significantly higher in the Wnt3a-knockdown cells compared with the control cells, indicating that knockdown of Wnt3a may promote Col2 expression. Consequently, Wnt3a was indicated to be an important factor in cartilage homeostasis, and Wnt3a knockdown may serve as a novel method for OA therapy.
骨关节炎（OA）是一种由软骨降解引起的慢性疾病，目前尚无有效的方法来阻止这种疾病的进展；基因治疗是一种相对较新的治疗关节炎的方法。软骨基质中II型胶原蛋白（Col2）表达降低是OA发生发展的一个重要因素，而Wnt3a在软骨稳态中发挥着重要作用。本研究评估了Wnt3a基因敲低是否能促进软骨细胞中Col2的表达。采用慢病毒导入的小干扰RNA敲低原代大鼠软骨细胞中Wnt3a的表达，然后用白细胞介素-1β处理建立OA软骨细胞模型。使用逆转录定量PCR、蛋白质印迹法和免疫细胞化学分析靶基因（Wnt3a、Col2、基质金属蛋白酶-13和β-连环蛋白）的表达。与其他对照组相比，Wnt3a基因敲低的细胞中基质金属蛋白酶-13和β-连环蛋白的表达明显减少。与对照细胞相比，Wnt3a基因敲低的细胞中Col2的表达明显更高，表明Wnt3a基因敲低可能促进Col2的表达。因此，Wnt3a被认为是软骨稳态的一个重要因素，Wnt3a基因敲低可能成为一种新的OA治疗方法。
