MicroRNA-146a-3p as an alternative to anti-IL-6 monoclonal antibody therapy: Intra-articular liposome delivery for osteoarthritis treatment

Interleukin-6 (IL-6) is a crucial inflammatory cytokine associated with chronic pain and cartilage degradation in osteoarthritis (OA). The binding of IL-6 to the IL-6 receptor (IL-6R) leads to homodimerization and the recruitment of glycoprotein 130 (gp130), subsequently activating the transcription factor signal transducer and activator of transcription 3 (STAT3) to initiate the downstream inflammatory cascade. Therefore, a therapy that targets the IL-6/IL-6R/STAT3 signaling axis shows promise for OA treatment. MicroRNAs (miRs) modulate messenger RNA in translational regulation, and dysregulation of miR-146a is noted in articular cartilage. In addition, miR-146a is also known to regulate IL-6 expression and affect OA-associated algesia. Bioinformatic analysis revealed that miR-146a-3p targets IL-6, IL-6R, gp130, and STAT3 simultaneously. Accordingly, we hypothesize that multipoint targeting the IL-6/IL-6R/STAT3 signaling axis through intra-articular injection of liposomal miR-146a-3p mimic might replace anti-IL-6 monoclonal antibody therapy and serve as a disease-modifying treatment for OA.