| Objective To investigate the effect of perindopril on the apoptosis and osteogenic differentiation of bone marrow mesenchymal stem cells (MSCs) induced by glucocorticoids (GCS), and to analyze the possible mechanism. Methods The MSCs were cultured in vitro and randomly divided into 5 groups: blank control group, dexamethasone group (DEX group, 106 mol/L DEX), low, medium and high dose perindopril groups (106 mol/L DEX solution + 0.01, 0.1, 1.0 μmol/L perindopril).MTT assay and flow cytometry were used to detect cell proliferation and apoptosis; Real-time fluorescent quantitative PCR, Western blot was used to detect the mRNA and expression of apoptosis related proteins cysteiny aspartate specific protease3 (cleaved Caspase-3), B-cell lymphoma-2 (Bcl-2), Bcl-2-associated X protein (Bax), osteogenic differentiation specific proteins alkaline phosphatase (ALP), type Ⅰcollagen (Collagen I), osteopontin (OPN), Notch pathway ligands (JAG1, JAG2), transmembrane receptor proteins (Notch1, Notch2), and downstream target genes (Hes1, hey1). Results Compared with those in the blank control group, the proliferation inhibition rate and apoptosis rate of MSCs, Bcl-2, cleaved-caspase-3 mRNA and protein expression in dex group were significantly increased (P<0.05), the mRNA and protein expression of ALP, Collagen I, OPN, Bax, JAG1, JAG2, Notch1, Notch2, Hes1, Hey1 was significantly decreased (P<0.05);compared with those in DEX group, the proliferation inhibition rate and apoptosis rate of MSCs, Bcl-2, cleaved-caspase-3 mRNA and protein expression in low, medium and high dose perindopril groups were significantly decreased (P<0.05),the mRNA and protein expression of ALP, Collagen I, OPN, Bax, JAG1, JAG2, Notch1, Notch2, Hes1, Hey1 was significantly decreased (P<0.05), in a dose-dependent manner. Conclusion Perindopril can inhibit DEX-induced apoptosis and promote osteogenic differentiation of MSCs. The mechanism may be related to the activation of Notch pathway. |