Osteoarthritis (OA) is a slow-progressing degenerative joint disease mainly characterized by progressive cartilage loss and subchondral bone remodeling. Osteopontin (OPN) is a matrix extracellular glyco-phosphoprotein capable of regulating the expression levels of multiple factors linked with OA pathogenesis. This study explores the upstream regulatory molecular mechanism of OPN on proliferation and apoptosis of human chondrocytes in OA. Chondrocytes were isolated from OA cartilage and identified by toluidine blue staining and immunofluorescent staining of type II collagen. An MTT assay was used for cell viability, and a BrdU assay was applied for DNA synthesis. Cell apoptosis was detected by a flow cytometry assay. A lncRNA MIAT/miR-181a-5p/OPN axis regulating OA chondrocyte proliferation and apoptosis were identified. miR-181a-5p directly targeted OPN and inhibited OPN expression in OA chondrocytes. miR-181a-5p overexpression inhibited OA chondrocyte viability, suppressed DNA synthesis, and promoted apoptosis. OPN overexpression exerted opposite effects on OA chondrocytes and significantly attenuated the roles of miR-181a-5p overexpression in OA chondrocytes. A total of six long non-coding RNAs (lncRNAs) were predicted to target miR-181a-5p, and MIAT was the most up-regulated in OA cartilage tissues among the six lncRNAs. Through direct targeting, MIAT inhibited miR-181a-5p expression. MIAT silencing inhibited cell viability, suppressed DNA synthesis, and promoted cell apoptosis. Moreover, miR-181a-5p inhibition partially reversed the effects of MIAT silencing on OA chondrocytes. The lncRNA MIAT/miR-181a-5p/OPN axis could modulate OA chondrocyte proliferation and apoptosis. The comprehensive function of this axis on OA requires further in vivo and clinical investigations.

骨关节炎（OA）是一种进展缓慢的退行性关节疾病，主要以进行性软骨丧失和软骨下骨重塑为特征。骨桥蛋白 (OPN) 是一种基质细胞外糖磷蛋白，能够调节与 OA 发病机制相关的多种因子的表达水平。本研究探讨OPN对OA中人软骨细胞增殖和凋亡的上游调控分子机制。从 OA 软骨中分离出软骨细胞，并通过甲苯胺蓝染色和 II 型胶原蛋白的免疫荧光染色进行鉴定。MTT测定用于细胞活力，BrdU测定用于DNA合成。通过流式细胞术检测细胞凋亡。鉴定了调节 OA 软骨细胞增殖和凋亡的 lncRNA MIAT/miR-181a-5p/OPN 轴。miR-181a-5p 直接靶向 OPN 并抑制 OA 软骨细胞中的 OPN 表达。miR-181a-5p 过表达抑制 OA 软骨细胞活力，抑制 DNA 合成并促进细胞凋亡。OPN 过表达对 OA 软骨细胞产生相反的影响，并显着减弱 miR-181a-5p 过表达在 OA 软骨细胞中的作用。预计共有六种长链非编码 RNA (lncRNA) 靶向 miR-181a-5p，在这六种 lncRNA 中，MIAT 在 OA 软骨组织中上调最多。通过直接靶向，MIAT 抑制了 miR-181a-5p 的表达。MIAT 沉默抑制细胞活力，抑制 DNA 合成，并促进细胞凋亡。此外，miR-181a-5p 抑制部分逆转了 MIAT 沉默对 OA 软骨细胞的影响。lncRNA MIAT/miR-181a-5p/OPN 轴可以调节 OA 软骨细胞增殖和凋亡。该轴对 OA 的综合作用需要进一步的体内和临床研究。