The diagnostic value of miR-4281 for knee osteoarthritis and its mechanism of action on the extracellular matrix of chondrocytes and apoptosis

Abstract Background The destruction of tissues such as bone and subchondral bone is an important pathological feature of knee osteoarthritis (KOA). Aim To explore the diagnostic value of serum miR-4281 and its mechanisms influencing KOA. Materials and methods The mRNA levels of miR-4281, SOX9, COL2A1, MMP3, MMP13 and BCL3 were detected by RT-qPCR. Pearson correlation was used to assess the correlation between serum miR-4281 and WOMAC score or BCL3. The receiver operating characteristic (ROC) curve was used to analyse the diagnostic efficacy of miR-4281 for KOA. Multivariate Logistic regression was used to assess the impact of miR-4281 on KOA. The dual luciferase reporter gene assay demonstrated the relationship between miR-4281 and BCL3. Annexin V-FITC/PI Apoptosis Kit was used to assess the apoptosis level of C28/I2 cells. Results In KOA patients, serum miR-4281 was significantly upregulated, while BCL3 was markedly downregulated. miR-4281 exhibited a positive correlation with the WOMAC score and demonstrated high diagnostic efficacy for KOA. 10 ng/mL IL-1β induced the expression of miR-4281, MMP3, and MMP13 in C28/I2 cells, as well as cell apoptosis, while inhibiting the expression of SOX9, COL2A1 and BCL3. miR-4281 inhibitors promote SOX9 and COL2A1 expression while suppressing MMP3 and MMP13 expression as well as apoptosis. Silencing BCL3 reversed the mitigating effects of miR-4281 inhibitors on IL-1β-induced extracellular matrix (ECM) degradation and apoptosis in C28/I2 cells. Conclusion miR-4281 has a good diagnostic efficacy for KOA and it alleviates the ECM degradation and apoptosis of chondrocytes induced by IL-1β by targeting BCL3.