SPARC deficiency impairs rotator cuff tendon development and hinders post-injury repair through the Wnt pathway

Purpose This study aimed to elucidate the role of secreted protein acidic and rich in cysteine (SPARC) in rotator cuff tendon development, degeneration, and repair, with a specific focus on its interaction with the Wnt signaling pathway. Methods We established a rat supraspinatus detachment model and performed localized adeno-associated virus (AAV)-mediated knockdown of SPARC. Structural and functional outcomes were evaluated using histological staining, immunohistochemistry, immunofluorescence, and µCT analysis. Molecular profiling focused on Wnt pathway components. Behavioral assays, including pain threshold and motor function tests, were conducted to assess physiological responses after injury. Results SPARC deficiency delayed tendon maturation, disrupted collagen alignment, impaired tendon-bone integration, and increased susceptibility to injury. Molecular analysis revealed significant downregulation of Wnt3, Wnt5, and β-catenin. Functionally, SPARC-deficient rats displayed heightened pain sensitivity, impaired motor recovery, defective vascular remodeling, and enhanced adipogenesis compared with controls. Conclusion SPARC is essential for maintaining tendon homeostasis and promoting tendon-bone healing after injury, partly through regulation of Wnt signaling. These findings establish a reliable preclinical RCI model and identify SPARC as a promising therapeutic target and biomarker for tendon degeneration and repair.