MiR 26a as a stage-dependent biomarker and therapeutic regulator of inflammation in knee osteoarthritis

BACKGROUND Osteoarthritis of the knee (KOA) is a prevalent degenerative joint disorder characterised by progressive cartilage breakdown and chronic inflammation. miRNAs have emerged as key regulators of gene expression in cartilage homeostasis and inflammatory signaling. Two of these, miR-26a2 and its isoform miR-26a5, play a role in regulating the NF-κB-mediated catabolic pathway. AIM To explore the distinct functions of miR-26a2 and miR-26a5 in the inhibition of inflammatory gene expression in KOA. METHODS A cross-sectional study was conducted from June to September 2023, with 100 patients (50 with KOA and 50 healthy controls and 50 KOA patients (grade 1, 2 and 3 according to the Kellgren-Lawrence criteria). Serum samples were analysed for miR-26a2, miR-26a5, and inflammatory genes (NF-κB , COX-2 , MMP-13 , NOS2 ) using reverse transcriptase quantitative PCR. Data were analysed using t -tests, ANOVA and correlation mapping to determine the relationship between miRNA levels and inflammatory gene expression. RESULTS MiR-26a2 levels were stable across all groups, indicating a minimal role in KOA. However, miR-26a5 showed a progressive decrease, reaching its lowest in grade-3 patients. Diminished miR-26a5 expression was negatively associated with upregulated NF-κB, COX-2, MMP-13 and NOS2, suggesting a protective effect against inflammation-mediated cartilage destruction. Correlation analyses confirmed significant associations between miRNA expression and upregulation of inflammatory genes, especially in advanced KOA. CONCLUSION MiR-26a5 is a stage-specific biomarker and modulator of inflammatory processes in KOA, while miR-26a2 is not. Downregulation of miR-26a5 enhances NF-κB-driven catabolic pathways, driving KOA progression. While the study has limitations in terms of sample size and duration, it highlights the role of miR-26a5 in maintaining cartilage homeostasis and as a potential biomarker for KOA severity.