To investigate the expressions of microRNA-138 (miR-138) and hypoxia inducible factor-2α (HIF-2α) in synovial membrane and synovial fluid of patients with knee osteoarthritis (KOA) and their clinical significances.

From March 2016 to October 2019, 80 patients with KOA treated by Beijing Luhe Hospital Affiliated to Capital Medical University were treated as KOA group, excluding immune diseases such as rheumatoid arthritis, ankylosing spondylitis, joint diseases combined with other types, serious osteoporosis, and 76 cases of meniscus injury during the same period were selected as the control group. The expression levels of miR-138 and HIF-2α in synovium and synovial fluid of the two groups were examined, and compared by t test. The expression levels of miR-138 and HIF-2α in synovium and synovial fluid of KOA patients with different Kellgren-Lawrence(K-L) grades were compared by one-way ANOVA, and the Pearson method was used to analyze the relationship between the expression levels of miR-138 and HIF-2α in synovial membrane and synovial fluid of KOA patients. The diagnostic value of miR-138 and HIF-2α in synovial membrane and synovial fluid were analyzed. The expression levels of miR-138 and HIF-2α in normal chondrocytes and KOA chondrocytes were detected, and the effect of miR-138 silencing/overexpression on HIF-2α expression in KOA chondrocytes was analyzed.

The expression of miR-138 in synovial membrane, synovial fluid and chondrocytes of KOA patients was significantly lower than that of control group (t=8.324, 9.054, 2.613, all P<0.05), and the expression of HIF-2α mRNA was significantly higher than that of control group (t=8.219, 10.685, 2.576, all P<0.05). The expression level of miR-138 in synovium membrane and synovial fluid of patients with grade III and IV KOA was significantly lower than that of patients with grade II KOA (t_Ⅲ-Ⅱ=3.731, 5.120, t_Ⅳ-Ⅱ=7.878, 10.511, all P<0.05). The expression level of miR-138 in synovium membrane and synovial fluid of patients with grade IV KOA was significantly lower than that of patients with grade III KOA (t =4.997, 6.518, all P<0.05); the expression level of HIF-2α in synovium membrane and synovial fluid of patients with grade III and IV KOA was significantly higher than that of patients with grade II KOA (t_Ⅲ-Ⅱ =3.462, 4.057, t_Ⅳ-Ⅱ =5.731, 6.528, both P<0.05). The expression of HIF-2α in synovium membrane and synovial fluid of patients with grade IV KOA was significantly higher than that of patients with grade III KOA (t =2.855, 3.135, both P<0.05); the areas under curve (AUC) of miR-138 in synovial membrane and synovial fluid for KOA diagnosis were 0.812 and 0.860, and the truncation values were 0.93 and 0.81, respectively. The corresponding sensitivities were 86.3%, 81.3%, and the specificities were 72.4% and 81.6%. The AUCs of HIF-2α in synovial membrane and synovial fluid in diagnosis of KOA were 0.890 and 0.881, and the cut-off values were 1.43 and 1.44, respectively. The corresponding sensitivities were 81.3%, 76.3%, and the specificities were 85.5% and 86.8%. The AUCs of miR-138 and HIF-2α in synovial membrane and synovial fluid were 0.924 and 0.929, respectively. The sensitivities were 87.5% and 90.0% respectively, and the corresponding specificities were 90.8% and 88.2% respectively; the expression level of miR-138 in miR-138-siRNA group was significantly lower than that in blank group and NC-siRNA group (t=2.895, 2.893, both P<0.05), HIF-2α mRNA expression level was significantly higher than that in blank group and NC-siRNA group (t=2.861, 2.717, both P<0.05); miR-138 expression level in miR-138-mimics group was significantly higher than that in blank group and NC-mimics group (t=2.731, 2.694, both P<0.05), and HIF-2α mRNA expression level was significantly lower than that in blank group and NC-mimics group (t=2.998, 3.112, both P<0.05).

The expression of miR-138 in synovium membrane and synovial fluid of the patients with KOA is low, and the expression of HIF-2α is high. There is a strong negative correlation between them, miR-138 may participate in the pathological process of KOA by regulating HIF-2α, and the combination of miR-138 and HIF-2α can effectively improve the diagnostic value of KOA.