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.