Effects of Regulating SPRY2 and miR-590-5p Expression on Autophagy in Human Osteoarthritis Model Chondrocytes

Osteoarthritis (OA) is a prevalent degenerative joint disease characterized by progressive cartilage destruction and loss of chondrocyte homeostasis. Although dysregulated autophagy contributes to OA pathogenesis, the molecular mechanisms governing autophagy-associated responses in chondrocytes remain incompletely understood. This study investigated the role of the miR-590-5p/SPRY2 regulatory axis in an inflammatory OA microenvironment using IL-1β-induced C28/I2 human chondrocytes. An in vitro OA model was established by treating C28/I2 cells with IL-1β. The expression of miR-590-5p and SPRY2 was evaluated using quantitative PCR and Western blotting. Gain- and loss-of-function approaches were employed to assess the effects of SPRY2 and miR-590-5p on the autophagy-associated markers Beclin-1 and LC3-II, as well as the survival-related protein Bcl-2. Bioinformatic analysis and rescue experiments were used to investigate the regulatory relationship between miR-590-5p and SPRY2. IL-1β treatment significantly increased miR-590-5p expression while reducing SPRY2 mRNA and protein levels (P < 0.05). SPRY2 overexpression markedly decreased Beclin-1 and LC3-II expression, with reductions of approximately 65% and 77%, respectively (P < 0.05). In contrast, miR-590-5p overexpression increased Beclin-1, LC3-II, and Bcl-2 expression, whereas inhibition of miR-590-5p reversed these effects and restored SPRY2 expression. Functional analyses supported SPRY2 as a putative downstream regulatory target of miR-590-5p. These findings identify the miR-590-5p/SPRY2 axis as an important regulator of autophagy-associated marker expression and chondrocyte survival under inflammatory conditions and suggest its potential relevance as a therapeutic target in OA.