Identification of the miR-1287-5p/PIK3R3 regulatory axis in knee osteoarthritis: clinical correlation and functional validation

Osteoarthritis (OA) is a debilitating degenerative joint disorder characterized by progressive cartilage destruction and chronic inflammation, with no curative therapies available. To investigate the clinical significance and functional mechanism of miR-1287-5p in knee OA. A total of 130 primary knee OA patients and 100 age- and sex-matched healthy controls were enrolled. Serum miR-1287-5p levels were detected by RT-qPCR, and their correlations with clinical parameters were analyzed. In vitro OA model was established by stimulating human chondrocytes with IL-1β. Dual-luciferase reporter assay and RNA immunoprecipitation were performed to verify the target relationship between miR-1287-5p and PIK3R3. Rescue experiments were conducted to confirm the functional axis. Serum miR-1287-5p was markedly upregulated in OA patients, and its expression was positively correlated with disease severity, pain scores, cartilage degradation markers, and pro-inflammatory cytokines. ROC analyses demonstrate that serum miR‑1287‑5p shows promising diagnostic potential for distinguishing OA patients from healthy subjects and for discriminating advanced‑stage from early‑stage knee OA, based on our single‑centre observational cohort. Mechanistically, miR-1287-5p directly targeted and negatively regulated PIK3R3 expression in chondrocytes. Inhibition of miR-1287-5p relieved IL-1β-evoked cellular dysfunction, aberrant apoptosis and excessive secretion of matrix catabolic enzymes plus pro-inflammatory factors, and these mitigating effects were offset the knockdown of PIK3R3. Serum miR-1287-5p serves as a promising non-invasive biomarker for OA diagnosis and severity assessment. miR-1287-5p promotes chondrocyte injury and inflammation via targeting PIK3R3.