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Effects and mechanism of olanzapine on the adipose differentiation of mouse bone marrow mesenchymal stem cells
JI Chen-yanLI Yong-hai*LI MengYANG Hai-jie FENG Zhi-wei
Acta Anatomica Sinica ›› 2016 ›› Issue (3) : 341-347.
Effects and mechanism of olanzapine on the adipose differentiation of mouse bone marrow mesenchymal stem cells
Objective To investigate the effects of olanzapine on the adipose differentiation and mechanism of mouse bone marrow mesenchymal stem cells(BMSCs).
Methods MTT colorimetry was used for assaying different concentrations of olanzapine on the proliferation of mouse BMSCs. The morphology of cells was observed by Oil red O staining. The expressions levels of adipocyte markers αP2 and C/EBPβ were detected by Western blotting, mRNA expression levels of the related genes of Leptin, C/EBPα and TNF-α were analyzed by Real-time PCR. The protein expression of Akt signaling pathway related molecules and effects of phosphatidylinositol 3 kinase (PI3K)/Akt inhibitor on the differentiation of BMSCs were determined by Western blotting. Results The results of MTT colorimetry showed that 20μmol/L olanzapine had minimal toxicity on BMSCs. Oil red O staining showed that intracellular lipid droplets in the experimental group were significantly more than the control group. The results of Western blotting showed that the expression levels of αP2 and C/EBPβ increased by about 36%(P<0.01) and 25%(P<0.05) compared with the control group respectively. The results of Real-time PCR showed that the expression levels of adipogenic genes Leptin, C/EBPα and TNF-α significantly increased than the control group, increased about 68%（P<0.001）,79%（P<0.01）and 60%（P<0.01）respectively. The expression levels of p-Akt were significantly higher than the control group, the expression of glycogen synthase kinase 3β(GSK-3β) with the increase of p-Akt expression gradually reduced. The expression levels of αP2 and C/EBPβ were inhibited after BMSCs were pretreated with PI3K/Akt inhibitor (LY294002). Oil red O staining results showed fat droplets in cells also decreased significantly. Conclusion Olanzapine may elevate the expression level of p-Akt of PI3K/AKT signaling pathway to promote the adipogenic differentiation of mouse BMSCs.
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Supported by Cooperation project of Chinese Academy of Sciences of Henan Province;Intramural science fostering foundation of Xinxiang Medical University;Graduate student research and innovation project
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