Study on the regulation of Nrf2/HO-1 signaling pathway mediated by carnosol in the treatment of osteoporosis
Objective To study the effect of carnosol on osteogenic differentiation of MC3T3-E1 cells under oxidative stress and its mechanism,and to expound the potential of carnosol in the treatment of osteoporosis.Methods MC3T3-E1 cells were treated with different concentrations of carnosol(0.0,1.0,2.5,5.0,10.0,25.0,50.0,and 100.0 μmol/L)for 24 h,the effects on osteoblast proliferation were analyzed,and the optimal concentration of carnosol was selected for follow-up experiments.The cells were divided into control group(no treatment),model group(250.0 µmol/L H2O2 intervention),carnosol low concentration group(250.0 μmol/L H2O2+2.5 μmol/1 carnosol)and carnosol high concentration group(250.0 μmol/L H2O2+5.0 μmol/L carnosol),each group was treated for 24 h.Reactive oxygen species(ROS),malondialdehyde(MDA),alkaline phosphatase(ALP)activity,mineralized area ratio,Runx2,Osterix,and COL1A mRNA expressions,and Nrf2,HO-1,and SOD2 mRNA and protein expressions were compared among all groups.Results The concentration of 2.5 μmol/L and 5.0 µmol/L carnosol were selected for follow-up experiments.Compared with control group,ROS and MDA contents,Nrf2 and HO-1 mRNA and protein expressions were increased;ALP activity,mineralized area ratio,Runx2,Osterix,COL1A mRNA expressions,and SOD2 mRNA and protein expressions were decreased in model group(P＜0.01).Compared with model group,ROS and MDA contents were decreased;ALP activity,mineralized area ratio,Runx2,Osterix and COL1A mRNA expressions,and Nrf2,HO-1 and SOD2 mRNA and protein expressions were increased in low and high concentration groups(P＜0.01).Compared with carnosol low concentration group,ALP activity,mineralized area ratio,and HO-1 protein expression were increased in carnosol high concentration group(P＜0.05);there were no significant differences in ROS,MDA contents,Runx2,Osterix,COL1A,HO-1 mRNA expressions,and Nrf2,SOD2 mRNA and protein expressions between carnosol low and high concentration groups(P＞0.05).Conclusion Carnosol can regulate the oxidative stress of MC3T3-E1 cells by activating the Nrf2/HO-1 signalling pathway,which can promote osteogenic differentiation and alleviate the imbalance of bone metabolism in the process of osteoporosis.
万方数据
维普
