The Impact of miR‐455‐5p Modulation on Enhancing Tendon‐Bone Interface Healing and Macrophage Polarization Following Anterior Cruciate Ligament Reconstruction

ABSTRACT MicroRNAs (miRNAs) have emerged as key regulators in physiological and pathological processes, including tendon‐bone healing after anterior cruciate ligament reconstruction (ACLR). This study identifies the upregulation of miR‐455‐5p in tendon‐bone interface tissues during early postoperative periods. Using a mouse ACLR model, we explored the impact of miR‐455‐5p inhibition on macrophage polarization and tendon‐bone healing. Our in vitro and in vivo investigations demonstrate that blocking miR‐455‐5p promotes M2 macrophage polarization and anti‐inflammatory cytokine production. Mice treated with miR‐455‐5p inhibitor exhibited enhanced bone formation, mature interface tissue, and superior mechanical properties. This study attributes the therapeutic benefits to miR‐455‐5p's interaction with the suppressor of cytokine signaling 3 (SOCS3), influencing the JAK2/STAT3 signaling pathway. These insights advance the understanding of miRNA‐mediated regulation in ACLR recovery, highlighting potential therapeutic targets for improving post‐surgical outcomes.