IL-1α induces apoptosis and inhibits the osteoblast differentiation of MC3T3-E1 cells through the JNK and p38 MAPK pathways

作者：Chun Guo, Xuguang Yang, Fei Wang, Xuyuan Ma · 发表于：International Journal of Molecular Medicine · 年份：2016 · DOI：10.3892/ijmm.2016.2606 · 被引用次数：50 · 研究领域：Bone Metabolism and Diseases、NF-κB Signaling Pathways、Cell death mechanisms and regulation

Interleukin (IL)-1 is a proinflammatory cytokine that plays important roles in inflammation and host responses to infection. The present study aimed to evaluate the effects of IL-1α on the apoptosis and differentiation of osteoblasts, and to elucidate the mechanism responsible for these effects in the osteoblast‑like cell line MC3T3-E1. The MC3T3-E1 cells were non-treated or treated with IL-1α. Following treatment, cell viability, alkaline phosphatase (ALP) activity and caspase-3 activity were evaluated. The expression of osteoblast-specific genes as well as Bax, Bcl-2 and caspase-3 were determined by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). The protein levels of Bax, Bcl-2, caspase-3 and the phosphorylation of mitogen-activated protein kinases (MAPKs, also known as MAP kinases) were evaluated using western blot analysis. The MAPK signaling pathway was blocked by pre-treatment with MAPK inhibitors SB203580, PD98059 and SP600125. IL-1α treatment induced a significant decrease in cell viability and ALP activity in the MC3T3-E1 cells. IL-1α also significantly decreased the mRNA expression and protein levels of osteoblast-related genes in the MC3T3-E1 cells. On the other hand, IL-1α significantly upregulated the mRNA expression and protein levels of Bax and caspase-3 as well as caspase-3 activity, whereas Bcl-2 expression was decreased in the MC3T3-E1 cells. Furthermore, IL-1α activated the apoptotic signaling pathway by increasing the phosphorylati...