Strontium ranelate-induced anti-adipocytic effects are involved in negative regulation of autophagy in rat bone marrow mesenchymal stem cells.

PURPOSES: Strontium ranelate (SrRN) is a novel and effective anti-osteoporotic drug used to promote bone formation and restrain bone resorption. However, studies of the effects and mechanism of SrRN on adipocytic differentiation from bone marrow mesenchymal stem cells (BMMSCs) remain limited.
METHODS: The cytoactivity of BMMSCs was analyzed by CCK-8 and annexin V-FITC/PI kit. Then the differentiation efficiency was analyzed by Oil Red O staining and western blotting. The level of autophagy was evaluated by immunofluorescence and western blotting. The autophagy inhibitor chloroquine and the selective Akt antagonist API-2 were used to study the relationship between autophagy regulation and adipocytic differentiation. Finally variations in β-catenin protein levels were also analyzed by western blotting, as were proteins related with autophagy and differentiation signaling pathways.
RESULTS: SrRN had no influence on the vatility of BMMSCs (bone marrow mesenchymal stem cells) and exhibited anti-adipocytic effects in dose-dependent manner. At the early stage of adipocytic differentiation, autophagy level significantly increased and SrRN inhibited the variation tendency. Then we detected the PPAR-γ and β-catenin variation when applied with autophagy inhibitor CQ (chloroquine) and the same way, after Akt selective inhibitor applied in the test, the effect of SrRN was compromised. At last, we detected the increased phosphorylation of Akt-related pathway at 1.00 mM concentration of SrRN in comparison with the adipocytic induction.
CONCLUSIONS: SrRN could disturb the process of adipocytic differentiation of BMMSCs and interfere with the variation tendency of autophagy level after adipocytic induction in Akt-dependent manners.