Extracellular Vesicles Transfer Tfam Mrna To Promote Bone Remodeling.

This study aims to elucidate the mechanisms underlying mesenchymal stem cells (MSCs)-mediated regulation of Treg/Th17 balance through extracellular vesicles (EVs)-modulated mitochondrial function, with the goal of identifying novel therapeutic targets to enhance MSC-driven bone remodeling and regeneration. Fluorescent labeling combined with FC analysis was used to label and locate TFAM mRNA. WB was used to assess TFAM levels. mitochondrial DNA(mtDNA) copy number was quantified via qRT-PCR. ROS level was measured by DCFH-DA.A periodontal defect model was established in eighteen male SD rats. TFAM mRNA-PDLSCA and TFAM mRNA-OE-PDLSCA were transplanted into the defect sites. Bone mineral density and defect volume were evaluated via Micro-CT. ROS/ERK/HIF-1α level were quantified by WB. IHC staining was performed to assess the expression of Treg,Th17,IL-17,IL-10,TGF-β,RANKL,OPG,TRAP. EVs mediated the intercellular transfer of TFAM mRNA.Following the translation of TFAM mRNA, the upregulated TFAM protein expression enhanced mtDNA copy number and reduced ROS production. The diminished ROS level attenuated ERK activation, thereby suppressed HIF-1α expression. HIF-1α shifted T cell metabolism from glycolysis to oxidative phosphorylation, ultimately promoted Treg differentiation and restored Treg/Th17 balance. Our findings suggest that MSCs-derived EVs transfer TFAM mRNA from MSCs to T cells. Following translation, the TFAM protein regulates T cell metabolic patterns by inhibiting the ROS-ERK-HIF-1α signaling pathway, thereby modulating the Treg/Th17 balance.