Exploring the Therapeutic Potential of MIR-140-3p in Osteoarthritis: Targeting CILP and Ferroptosis for Novel Treatment Strategies

Abstract

Osteoarthritis (OA) is a prevalent and debilitating joint disorder that affects millions of individuals worldwide, severely impairing mobility, independence, and quality of life. Emerging evidence suggests that ferroptosis is a critical factor in OA pathogenesis. However, its precise involvement and underlying mechanisms remain poorly understood. In this study, we first identified that cartilage intermediate layer protein (CILP) mediates the regulation of ferroptosis-related genes in OA through hdWGCNA analysis combined with single-cell RNA sequencing. Further investigation revealed a significant upregulation of CILP protein expression in C28/I2 cells under LPS induction. Mechanistically, bioinformatics analysis identified differentially expressed miRNAs; qRT-PCR combined with a dual-luciferase experiment revealed that miR-140-3p was downregulated and directly targets CILP. Experimental data further demonstrated that miR-140-3p regulates ferroptosis, inflammation, and oxidative stress by targeting CILP. These findings offer valuable insights into the molecular mechanisms of the miR-140-3p/CILP axis in regulating ferroptosis, inflammation, and oxidative stress, thus providing a foundation for developing therapeutic strategies for OA.