Mechanism Research Of Kartogenin Enhancing Antioxidant Functions And Promoting Osteogenesis In Mesenchymal Stem Cells Through SIRT1/AMPK Pathway

[Objective]:Osteoarthritis(OA)is a chronic degenerative joint disease that involves both articular cartilage and subchondral bone.In recent years,Kartogenin,a small molecule synthesized by foreign researchers,has been shown to increase the chondrogenic differentiation of mesenchymal stem cells(MSCs)and promote cartilage repair.However,other effects of Kartogenin such as osteogenic effects have not yet been reported.This article aims to investigate the effects of Kartogenin on the antioxidative function and osteogenic differentiation of bone marrow mesenchymal stem cells(BM-MSCs).[Methods]:Human adult BM-MSCs were treated with different concentrations of Kartogenin(10-8 M to 10-6 M)and Cell Count Kit-8 assay was used to determine cell proliferation.Intracellular reactive oxygen species and levels of intracellular antioxidant enzymes were evaluated to detect cellular antioxidant changes.The effect on osteogenic differentiation of BM-MSCs was estimated by Alizarin Red staining,Western-blot and real-time reverse transcription polymerase chain reaction(RT-PCR).The potential mechanism was also analyzed.[Results]:The results indicated that treatment with Kartogenin improved cell proliferation and attenuated intracellular ROS.The levels of antioxidant enzymes and osteogenic differentiation of BM-MSCs were improved by Kartogenin in a dose-dependent manner.Furthermore,we also found the up-regulation of silent information regulator type 1(SIRT1)and increased phosphorylation of Adenosine 5'-monophosphate activated protein kinase(AMPK),which were estimated by Western-blot and PCR.Inhibition of SIRT1 by SIRT1 inhibitor attenuated the antioxidant and osteogenic differentiation effect of Kartogenin on BM-MSCs.[Conclusion]:In conclusion,our results proved that Kartogenin could improve intracellular antioxidant capacities and promoted osteogenic differentiation of BM-MSCs by mediating the SIRT1/AMPK signaling pathway.