INTRODUCTION In our study we aimed to investigate the mechanism of Wnt inhibitory factor 1 (WIF1) on regulating chondrocyte proliferation and apoptosis via reactive oxygen species (ROS) and the Wnt/βcatenin signaling pathway in osteoarthritis (OA). MATERIAL AND METHODS Osteoarthritis chondrocytes were treated with interleukin 1β (IL-1β) to simulate an inflammatory condition. Quantitative real-time polymerase chain reaction (qRT-PCR) and western blot were applied for detecting WIF1 expression in OA chondrocytes. MTT assay and flow cytometry were carried out to analyze the cell proliferation and apoptosis. Content of ROS was detected using flow cytometry, and activity of the Wnt/βcatenin signaling pathway was detected using immunofluorescence, western blot and luciferase reporter assay. Western blot and enzyme-linked immunosorbent assay (ELISA) were performed to detect the expression of apoptosis-related proteins and secretion of matrix metalloproteinases (MMPs). RESULTS WIF1 expression in OA chondrocytes was significantly lower than in normal chondrocytes. After WIF1 cDNA transfection, the aberrantly high ROS level in OA chondrocytes was down-regulated, which led to the increase of proliferation and reduction of apoptosis. The Wnt/βcatenin signaling pathway was suppressed by WIF1 overexpression and the secretion of MMPs was therefore reduced. CONCLUSIONS Up-regulation of WIF1 would promote proliferation and suppress apoptosis of OA chondrocytes through eliminating ROS production and reduce secretion of MMPs via blocking the Wnt/βcatenin signaling pathway.

中文翻译：

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Wnt抑制因子1在骨关节炎中的作用机制研究。

引言 在我们的研究中，我们旨在研究 Wnt 抑制因子 1 (WIF1) 在骨关节炎 (OA) 中通过活性氧 (ROS) 和 Wnt/βcatenin 信号通路调节软骨细胞增殖和凋亡的机制。材料和方法 用白细胞介素 1β (IL-1β) 处理骨关节炎软骨细胞以模拟炎症状态。定量实时聚合酶链反应 (qRT-PCR) 和蛋白质印迹用于检测 OA 软骨细胞中 WIF1 的表达。采用MTT法和流式细胞仪分析细胞增殖和凋亡。流式细胞仪检测活性氧含量，免疫荧光、蛋白质印迹和荧光素酶报告基因检测Wnt/βcatenin信号通路活性。进行蛋白质印迹和酶联免疫吸附试验（ELISA）以检测细胞凋亡相关蛋白的表达和基质金属蛋白酶（MMPs）的分泌。结果 OA 软骨细胞中 WIF1 的表达明显低于正常软骨细胞。转染WIF1 cDNA后，OA软骨细胞中异常高的ROS水平下调，导致增殖增加和细胞凋亡减少。WIF1 过表达抑制了 Wnt/βcatenin 信号通路，因此 MMPs 的分泌减少。结论 WIF1上调可通过消除ROS产生促进OA软骨细胞增殖和抑制凋亡，并通过阻断Wnt/βcatenin信号通路减少MMPs的分泌。