Effects Of Malondialdehyde And Methylglyoxal On Growth And Apoptosis Of Human Bone Marrow Mesenchymal Stem Cells

Reactive carbonyl species(RCS) are common intermediates of lipid peroxidation and non-enzymatic glycosylation(glycation).Even in healthy organism,there are amounts of RCS,particularly carbonyls with di- and multi-functional groups,including malondialdehyde(MDA), methylglyoxal(MGO),4-hydroxylnonenal,3-deoxyglucosone and oxalaldehyde.It has been reported that RCS are correlated with inhibition of enzymes,disturbance of immune functions and destruction of membranes.According to the carbonyl stress theory of aging,the carbonyl-amino reactions are inevitable biological side-reactions in the metabolism of the lipids and carbohydrates,which will cause a series of crosslinkings in vivo,damage biological macromolecules,such as protein, lipid and nucleic acid,and accelerate the aging process.Human bone marrow mesenchymal stem cells(hMSCs) are adult stem cells that have huge potential capacity of regeneration and differentiation.Numerous evidences have demonstrated that the hMSCs are involved in the process of self-renewal and renovation of damaged tissues,while its amount and function will decrease with the advance of age.As a result,it is associated with many age-related diseases including osteoarthritis,osteoporosis,atherosclerosis and diabetes.Intriguingly, both MDA and MGO,representive RCS and respective products of lipid peroxidation and glycation,have also been reported to accumulate during various age-related diseases and play a critical role in the pathophysiological of the diseases.Aiming to reveal the mechanism of carbonyl stress to hMSCs,the effects of MDA and MGO on proliferation and apoptosis of hMSCs were investigated in this study.The hMSCs were identified by cell differentiation,surface markers and morphologies.Then the hMSCs were cultured in DMEM treated with different concentrations of MDA and MGO,and the growth curves were estimated by cell counting,the cellular viability were detected by MTT (3-(4,5-dimethylthiazol-2-y1)-2,5-diphenyl tetrazolium bromide) assay and the apoptosis were analyzed by flow cytometry(FCM).The results showed that there were not significant effects on the growth and the apoptosis of hMSCs under low concentration of MDA and MGO. However,the higher concentrations of MDA and MGO resulted in significant dose-dependent decrease of the cell growth and viability, prolongation of the population doubling time and increase of the apoptosis.These findings indicated that both MDA and MGO could damage hMSCS and result in alternations of the growth,proliferation, metabolism and other functions,and the carbonyl stress might be an important reason for a series of age-related pathophysiological changes.