Mechanism Research Of Melatonin Improving The Antioxidant Function And Osteogenic Differentiation Of Bone Marrow Mesenchymal Stem Cells Through SIRT1/SOD2 Pathway

Objective:Periprosthetic osteolysis(Periprosthetic osteolysis,PPO)as the main reason for failure of prosthetic replacement has been widely studied in recent years.A large number of studies proven the role of melatonin(melatonin,MT)in anti-oxidative stress and promoting osteogenesis.The purpose of this study was to investigate whether melatonin enhances the anti-oxidant function and osteogenic differentiation ability of mesenchymal stem cells by mediating the SIRT1/SOD2 pathway.Methods:BMMSCs were co-cultured with 100?g/ml titanium particles,and melatonin(1?M,100?M)was added to intervene.The intracellular reactive oxygen species(ROS),The expressions levels of SIRT1 and antioxidant enzymes were analyzed for the effects of melatonin on oxidative stress,and the expression of alizarin red staining and osteogenesis-related markers was analyzed for the effects of melatonin on the osteogenic differentiation ability under titanium particle loading.At the same time,we established a mouse skull osteolysis model,and analyzed the therapeutic effect of melatonin on osteolysis by micro-CT analysis and tissue section staining.Results:The addition of melatonin under the load of titanium particles promoted the cell's proliferation ability,and the content of reactive oxygen species and superoxide in the cell decreased.RT-PCR and Western blot analysis showed that SIRT1 and SOD2 were significantly expressed Up-regulated and enhanced osteogenic differentiation of BMMSCs cells.The therapeutic effect of melatonin was reconfirmed in the aunt's skull osteolysis model.Conclusion:Melatonin enhances the anti-oxidation function of mesenchymal stem cells and promotes osteogenic differentiation by mediating SIRT1/SOD2 pathway.