Metformin alleviates hyperglycemia-induced apoptosis and differentiation suppression in osteoblasts through inhibiting the TLR4 signaling pathway

Publication date: Available online 7 November 2018Source: Life SciencesAuthor(s): Lifeng Zheng, Ximei Shen, Junjian Ye, Yun Xie, Sunjie YanAbstractAimsMetformin was found to protect against hyperglycemia-induced injury in osteoblasts, but the cellular mechanisms involved remain unclear. Therefore, the aim of this study was to determine the effect of metformin on hyperglycemia-induced apoptosis and differentiation suppression in osteoblasts and to explore its relationships with the TLR4 signaling pathway.Main methodsA mouse osteoblast cell line, MC3T3-E1, and a diabetic rat model were used to survey the protective effects of metformin on hyperglycemia-induced injury. TLR4 expression was altered using small interfering (si)RNA and lentivirus-mediated TLR4 overexpression. LPS was used as a specific TLR4 activator, and CLI-095 was used as a TLR4 inhibitor.Key findingsMetformin improved osteoblast differentiation, reduced apoptosis in hyperglycemic osteoblasts, and inhibited TLR4, MyD88 and NF-κB expression in a dose-dependent manner. Down-regulating the expression or inhibiting the activity of TLR4 enhanced these protective effects of metformin on osteoblast differentiation, cell viability and cell apoptosis in hyperglycemic conditions, whereas up-regulating the expression or activating the activity of TLR4 had the opposite effects. Activating NF-κB suppressed the protective effects of metformin, while inhibiting NF-κB activity had the opposite effects. Metformin increased ALP...
Source: Life Sciences - Category: Biology Source Type: research