LncRNA CRNDE regulates the differentiation of tendon-derived stem cells and enhances rotator cuff injury repair by modulating the miR-337/TGFBR2 axis.

The differentiation of stem cells into tendon cells plays a crucial role in the repair of rotator cuff injuries. Long non-coding RNAs (lncRNAs) are known to regulate tendon-derived stem cell (TDSC) differentiation during tendon injury; however, the specific mechanisms involving the lncRNA colorectal neoplasia differentially expressed (CRNDE) have not been fully elucidated. In this study, we successfully isolated and cultured TDSCs, and established a tenogenic differentiation model through ascorbic acid treatment. RNA sequencing analysis showed that ascorbic acid significantly upregulated CRNDE expression. Furthermore, CRNDE overexpression in TDSCs markedly enhanced tenogenic differentiation. Using bioinformatics analysis in combination with luciferase reporter assays, we demonstrated that CRNDE and transforming growth factor beta receptor 2 (TGFBR2) contain shared binding sequences for miR-337, suggesting a competitive regulatory interaction. Overexpression of miR-337 was found to inhibit CRNDE-induced tenogenic differentiation and reduce both TGFBR2 mRNA and protein levels. In contrast, CRNDE knockdown decreased TGFBR2 protein expression and impaired tenogenic differentiation of TDSCs. In a rat model of rotator cuff tear (RCT), transplantation of CRNDE-overexpressing TDSCs significantly enhanced functional recovery, an effect associated with upregulation of TGFBR2. Taken together, these results demonstrate that CRNDE promotes tenogenic differentiation and tendon-bone healing through modulation of the miR-337/TGFBR2 signaling axis.