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  • Title: MiR-378 overexpression attenuates high glucose-suppressed osteogenic differentiation through targeting CASP3 and activating PI3K/Akt signaling pathway.
    Author: You L, Gu W, Chen L, Pan L, Chen J, Peng Y.
    Journal: Int J Clin Exp Pathol; 2014; 7(10):7249-61. PubMed ID: 25400823.
    Abstract:
    Hyperglycemia is one of the possible causes for osteoporosis and bone fracture in diabetes mellitus. Here we modeled diabetes-induced osteoporosis in vitro using preosteoblastic cell line MC3T3-E1 and a diabetic mice model for in vivo studies. We found that in addition to reducing osteoblast viability and differentiation (mineralization), culture in elevated glucose down regulated microRNA-378 (miR-378) expression but ectopic miR-378 expression reversed the effects of high glucose. We identified caspase-3 (CASP3) as a target of miR-378 and showed that miR-378 repressed CASP3 mRNA and protein expression under high glucose condition. We further showed that both miR-378 expression and CASP3 silencing independently restored alkaline phosphatase (ALP) activity and the expression of osteoblastic differentiation markers Runt-related transcription factor 2 (Runx2), osteorix (Osx), collagen I (Col I), osteocalcin (OCN), and osteonectin (ON). We also found that under high glucose conditions miR-378 activated the PI3K/Akt signaling pathway and down regulated pro-apoptotic CytC, Apaf-1 and Bax proteins via the PI3K/Akt pathway. Collectively, these results suggest that miR-378 overexpression attenuates high glucose-suppressed osteogenic differentiation through targeting CASP3 and activating the PI3K/Akt pathway.
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