Targeting Caveolin-1 for enhanced rotator cuff repair: findings from single-cell RNA sequencing.

Abstract

Rotator cuff injury (RCI), a prevalent cause of shoulder pain and disability, often leads to significant functional impairments due to adipocyte infiltration into the damaged tissue. Caveolin-1 (Cav-1), a critical membrane protein, plays a significant role in adipocyte differentiation and lipid metabolism. This study utilized single-cell RNA sequencing (scRNA-seq) to investigate the heterogeneity of cell subpopulations in RCI tissues and assess the regulatory effects of Cav-1. The findings revealed that Cav-1 expression negatively correlates with adipogenic activity, and its modulation through exercise or targeted therapies can significantly reduce adipocyte infiltration and enhance tissue repair. Further, Cav-1 knockout and overexpression models demonstrated the protein's impact on key genes involved in adipocyte differentiation and lipid metabolism, such as Scd1, fatty acid synthase (FASN), and peroxisome proliferator-activated receptor gamma (Pparg). Animal studies corroborated these results, showing that exercise intervention increased Cav-1 expression, decreased adipocyte infiltration, and promoted structural repair. These insights suggest that targeting Cav-1 could offer a novel therapeutic strategy for improving RCI outcomes.