Mtor Modulates Bone Remodeling By Regulating Osteocyte Ferroptosis During Periodontitis

This study investigates mTOR's role in periodontitis-associated bone resorption and explores whether mTOR mediates osteocyte ferroptosis to drive this process. Experimental periodontitis was induced in C57BL/6 and mTOR-knockout mice(All the experimental procedures were approved by the Institutional Animal Care and Use Committee of Sun Yat-Sen University(No. SYSU-IACUC-2022-001675). In vitro, mTOR and Tsc1 were knocked down in MLO-Y4 osteocytes using lentiviral vectors, followed by P.g-LPS stimulation. Ferroptosis markers were analyzed via Western blot, immunofluorescence, and flow cytometry. A tri-culture system (MLO-Y4, RAW264.7, and MC3T3-E1 cells) assessed osteoclast differentiation and osteogenesis. Transcriptome sequencing identified key pathways. In vitro and vivo experiments demonstrated that mTOR knockdown inhibits osteocyte ferroptosis under inflammatory conditions by regulating iron metabolism and the redox system to reduce ROS production. Under inflammatory conditions, mTOR knockdown reduces the ability of osteocytes to induce osteoclast differentiation but does not enhance their osteogenic induction capacity. In vitro, GO functional enrichment of mTOR knockout was associated with redox reactions and cell adhesion, while KEGG pathway enrichment was related to the TNF and MAPK signaling pathways. mTOR exacerbates periodontitis bone loss by promoting osteocyte ferroptosis, highlighting its potential as a therapeutic target.