Revised: March 8, 2026
Accepted: May 26, 2026
Published online: July 18, 2026
Processing time: 142 Days and 17.2 Hours
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.
To explore the distinct functions of miR-26a2 and miR-26a5 in the inhibition of inflammatory gene expression in KOA.
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.
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.
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 car
Core Tip: MiR 26a5, identified as a stage-specific biomarker for osteoarthritis of the knee (KOA), has its levels inversely correlated with the NF-κB, COX 2, MMP 13 and NOS2 expression. In contrast to lowly involved miR 26a2, miR 26a5 protects against inflammation-induced cartilage degradation. Its loss of function speeds up the disease process, highlighting its therapeutic potential and utility in measuring the level of KOA, despite small sample sizes and short-term studies.