Mechanism of age-related changes of bone marrow mesenchymal stem cells in senile osteoporosis

Abstract

This study was carried out to explore the age-related changes of bone marrow mesenchymal stem cells (BMMSCs) in mice as well as the influence of autophagy on the age-related changes of BMMSCs. BMMSCs aging-associated protein acetylation P53, P21 and P16 expressions in young and senile mice, protein expression of telomerase reverse transcriptase (TERT) as well as reactive oxygen species (ROS) level were detected and compared; the expression of BMMSCs autophagy associated gene, autophagy related protein molecule and LC3 molecule were detected; the influence of differently concentrated rapamycin and 3-MA on BMMSCs autophagy level was observed to select effective concentrations; the influence of rapamycin and 3-MA on BMMSCs cell cycle-related gene expression, apoptosis related gene expression and ROS level were discussed. Results revealed that the senile BMMSCs group had higher acetylation P53, P21 and P16 expression and fluorescence intensity than the young group, but its TERT expression, Beclin1 and LC3 gene expression and fluorescence intensity were lower than the young group. Both rapamycin and 3-MA inhibited CyclinD1 (CCND1) and CyclinD2 (CCND2) expression. Rapamycin promoted the expression of apoptosis-related genes Caspase3 and Caspase8 in the senile group, while 3-MA inhibited them in both the young and senile groups. It can therefore be concluded that senile BMMSCs have multiple age-related changes, performing as decrease of osteogenic capability and multiplication capacity, increase of acetylation P53, P21 and P16 protein expression, apoptosis and ROS level as well as decrease of telomerase activity. Furthermore, the autophagy level in senile BMMSCs reduced compared with young cells; autophagy activation can decrease ROS level and autophagy suppression improves ROS level; and autophagy regulation affects cell cycle and apoptosis.