miR-548aj-3p and miR-3127-3p suppress RANKL-facilitated inflammatory cytokines and catabolic factor in osteoarthritis and rheumatoid arthritis

Osteoarthritis (OA) and rheumatoid arthritis (RA) are high prevalent joint diseases in global. The common pathological features include synovial inflammation, swelling, joint destruction, and bone remodelling. Arthritis development is associated with joint inflammation, particularly in inflamed synovial cells. Synovial inflammation, driven by cytokines such as interleukin-1 beta (IL-1ß) and interleukin-6 (IL-6), is a crucial factor in arthritis as it contributes to joint destruction. RANKL is a vital factor that is linked to the activity of osteoclasts and the erosion of bone. Increased levels of RANKL related with the proinflammatory cytokines and cartilage degradation enzymes expression, playing a role in the course of arthritis. Medicines for arthritis have been limited by side effects and individual variability in therapeutic response. More effective treatment and drug options are needed to improve disease progression. miRNAs directly modulate gene transcription as potential option for arthritis therapeutic. Our study revealed that RANKL stimulation in OA and RA synovial fibroblasts upregulated the expression of IL-1ß, IL-6 (pro-inflammatory cytokines) and MMP-13 (catabolic factor) by suppressing miR-548aj-3p and miR-3127-3p. Administration of miR-548aj-3p and miR-3127-3p mimics substantially inhibited the expression of IL-1ß, IL-6 and MMP-13. We propose a potentially efficacious miRNA therapeutic approach for the treatment of arthritis, with a specific focus on OA and RA. Overall design: To explore the therapeutic potential of miRNAs affected by RANKL in osteoarthritis (OA) and rheumatoid arthritis (RA), we isolated synovial fibroblasts from the knees of OA and RA patients and stimulated the cells with RANKL.We then conducted miRNA expression profiling analysis using data obtained from miRNA-seq of 4 different cell samples. We performed a comparative miRNA expression profiling analysis of miRNA-seq data for synovial fibroblasts with or without RANKL stimulation.