Exosomal miR-212-5p promotes tendon repair via targeting FOXO1 to activate PP1A/YAP1 signaling

Tendon injury, resulting from repetitive strain or acute trauma, often leads to pain, reduced mobility, and impaired healing due to the limited regenerative capacity of tendon tissue. Adipose-derived stem cells (ADSCs) exosomes show therapeutic promise, though their mechanisms are unclear. We demonstrated that ADSC-Exos delivers miR-212-5p to tendon-derived stem cells (TDSCs), thereby enhancing their proliferation, migration, and tenogenic differentiation. miR-212-5p directly suppresses forkhead box protein O1 (FOXO1) by binding to its 3'UTR. This downregulation relieves transcriptional repression of protein phosphatase 1A (PP1A), thereby increasing its expression and leading to dephosphorylation and activation of Yes-associated protein 1 (YAP1) signaling. In vivo, ADSC-derived exosomal miR-212-5p promotes tendon repair in male C57BL/6 mice by downregulating FOXO1 and activating YAP1 signaling. Taken together, these findings demonstrate that ADSC-derived exosomal miR-212-5p promotes tendon repair by downregulating FOXO1 to modulate the PP1A/YAP1 axis, highlighting a exosome-based regulatory mechanism and suggesting potential therapeutic targets for tendon injury management.