Bone Marrow Mesenchymal Stem Cells Rescue Tendon Injury by Regulating FTO‐Mediated m6A Methylation of ELOB

ABSTRACT

Bone marrow mesenchymal stem cells (BMSCs) prominent capacity for tissue repair and regenerative applications due to their multipotent differentiation potential and immunomodulatory activities. This study explores the function of BMSCs in tendon repair, with a particular focus on their regulatory effect on fat mass and obesity‐associated protein (FTO)‐mediated m6A methylation of Elongin B (ELOB). In this study, BMSCs were isolated from mice with experimental tendon injury and characterized by detecting the expression of surface biomarkers (CD90, CD44, CD29, CD34, CD45). The proliferation, migration, apoptosis, and intracellular reactive oxygen species (ROS) levels of tenocytes were assessed using CCK‐8 assay, wound healing assay, and flow cytometry. RT‐qPCR and Western blot analysis were applied to quantify gene and protein expression, respectively. Dual luciferase reporter assay and methylated RNA immunoprecipitation (MeRIP) were performed to verify the regulatory relationship between FTO and ELOB. Functional recovery of injured tendons in mice was evaluated via behavioral tests and hematoxylin and eosin (HE) histological staining. The results showed that BMSCs effectively facilitated tendon repair in the murine tendon injury model. The RNA demethylase FTO was markedly downregulated in injured tendon tissues, and its expression could be modulated by BMSCs. Mechanistically, BMSCs upregulated FTO to accelerate tenocyte proliferation and migration, and simultaneously suppress oxidative stress during tendon injury. FTO repressed ELOB expression through m6A modification. Functional assays further demonstrated that FTO improved tenocyte proliferation and migration, and alleviated oxidative stress by downregulating ELOB. In vivo assays validated that overexpression of FTO boosted tendon repair by reducing ELOB expression. In conclusion, BMSCs improve tendon repair by stimulating tenocyte proliferation and migration and alleviating oxidative stress. This protective mechanism is dependent on the regulation of FTO‐mediated m6A methylation of ELOB.