Extracellular Vesicles Secreted by TGF-1-Treated Mesenchymal Stem Cells Promote Fracture Healing by SCD1-Regulated Transference of LRP5.

Bone fracture repair is a multiphased regenerative process requiring paracrine intervention throughout the healing process. Mesenchymal stem cells (MSCs) play a crucial role in cell-to-cell communication and the regeneration of tissue, but their transplantation is difficult to regulate. The paracrine processes that occur in MSC-derived extracellular vesicles (MSC-EVs) have been exploited for this study. The primary goal was to determine whether EVs secreted by TGF-1-stimulated MSCs (MSC-EVs) exhibit greater effects on bone fracture healing than EVs secreted by PBS-treated MSCs (MSC-EVs). Our research was conducted using an bone fracture model and experiments, which included assays to measure cell proliferation, migration, and angiogenesis, as well as and gain/loss of function studies. In this study, we were able to confirm that SCD1 expression and MSC-EVs can be induced by TGF-1. After MSC-EVs are transplanted in mice, bone fracture repair is accelerated. MSC-EV administration stimulates human umbilical vein endothelial cell (HUVEC) angiogenesis, proliferation, and migration . Furthermore, we were able to demonstrate that SCD1 plays a functional role in the process of MSC-EV-mediated bone fracture healing and HUVEC angiogenesis, proliferation, and migration. Additionally, using a luciferase reporter assay and chromatin immunoprecipitation studies, we discovered that SREBP-1 targets the promoter of the SCD1 gene specifically. We also discovered that the EV-SCD1 protein could stimulate proliferation, angiogenesis, and migration in HUVECs through interactions with LRP5. Our findings provide evidence of a mechanism whereby MSC-EVs enhance bone fracture repair by regulating the expression of SCD1. The use of TGF-1 preconditioning has the potential to maximize the therapeutic effects of MSC-EVs in the treatment of bone fractures.