Dual evidence reveals the therapeutic efficacy of exosome-delivered miR-124-3p in spinal cord injury via a novel CTDSP1/WNT/β-catenin mechanism.

Abstract

Integrated preclinical systematic review and meta-analysis with basic experimental research. To evaluate the therapeutic efficacy of miR-124-3p in spinal cord injury (SCI) repair and elucidate its mechanism involving the CTDSP1/WNT/β‑catenin axis. University-based laboratory in Lanzhou, China. A meta‑analysis of five animal studies assessed the effects of miR‑124‑3p. In vitro, a lipopolysaccharide‑injured PC12 cell model was treated with exosomes derived from miR‑124‑3p‑overexpressing human umbilical cord mesenchymal stem cells. Mechanistic validation included dual‑luciferase reporter assay, qPCR, Western blot, and pathway inhibition/rescue experiments. The meta‑analysis showed that miR‑124‑3p significantly improved motor function, reduced glial scar marker GFAP and pro‑inflammatory cytokines, and increased neuronal/axonal markers (Map2, NF200, NeuN). Mechanistically, miR‑124‑3p directly targeted the 3'‑UTR of CTDSP1. Exosome‑delivered miR‑124‑3p downregulated CTDSP1, activated WNT/β‑catenin signaling, suppressed GFAP/CSPG, and promoted β‑tubulin III, NeuN, and NF200 expression. These effects were reversed by the WNT inhibitor MSAB and mimicked by a CTDSP1 inhibitor. miR‑124‑3p promotes SCI repair primarily by targeting CTDSP1 to activate the WNT/β‑catenin pathway, thereby inhibiting glial scarring and enhancing neuronal survival/regeneration. This mechanism supports the therapeutic potential of combined exosome and miRNA strategies.