Inhibition of microRNA‐27b‐3p relieves osteoarthritis pain via regulation of KDM4B‐dependent DLX5

Abstract Osteoarthritis (OA) represents a progressive degenerative disorder that predominantly affects the synovial membranes of joints. Recent studies have highlighted the significant role played by microRNAs (miRNAs) in OA development. The current study aimed to elucidate the underlying modulatory role of miR‐27b‐3p in the development of OA. The expression of miR‐27b‐3p in the OA patients and rat models post anterior cruciate ligament transection operation was measured using reverse transcription quantitative polymerase chain reaction, through which overexpressed miR‐27b‐3p was found in both of the samples. To further explore the miR‐27b‐3p functions in OA, western blot analysis, enzyme‐linked immunosorbent assay, and β‐galactosidase activity assay were conducted with the results showing that knockdown of miR‐27b‐3p promoted expression of the osteogenic differentiation markers while inhibiting expression of the adipogenic differentiation markers, inflammatory factors, and cellular senescence of bone marrow mesenchymal stem cells (BMSCs). After that, the interactions between miR‐27b‐3p, lysine Demethylase 4B (KDM4B), and Distal‐Less Homeobox 5 (DLX5) identified using dual‐luciferase reporter gene assay and ChIP assay revealed that miR‐27b‐3p inhibited KDM4B and further reduced expression of DLX5. Finally, the paw withdrawal threshold (PWT) and paw withdrawal latency (PWL) were assessed in rat models, and increased PWT and PWL were detected after miR‐27b‐3p silencing. In conclusion, suppression of miR‐27b‐3p could enhance KDM4B and DLX5 to alleviate OA pain, shedding light on a new potential therapeutic target for OA.