title: IL-1α induces apoptosis and inhibits the osteoblast differentiation of MC3T3-E1 cells through the JNK and p38 MAPK pathways.
abstract: 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 phosphorylation of c-Jun N-terminal kinase (JNK) and p38-MAPK, whereas it inhibited the phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2). Moreover, pre-treatment with MAPK inhibitors attenuated the phosphorylation of JNK, p38 and Bax expression enhanced by IL-1α. However, MAPK inhibitors markedly increased the protein expression of osteoblast-related genes and Bcl-xL in the MC3T3-E1 cells downregulated by IL-1α. Taken together, these findings suggest that IL-1α induces the apoptosis of osteoblasts and inhibits osteoblast differentiation by activating the JNK and the p38 MAPK pathways.
authors.affiliation: Department of Medicine, Luohe Medical College, Luohe, Henan 462002, P.R. China.
authors.forename: Chun
authors.initials: C
authors.lastname: Guo
authors.affiliation: Department of Medicine, Luohe Medical College, Luohe, Henan 462002, P.R. China.
authors.forename: Xu-Guang
authors.initials: XG
authors.lastname: Yang
authors.affiliation: Department of Medicine, Luohe Medical College, Luohe, Henan 462002, P.R. China.
authors.forename: Fei
authors.initials: F
authors.lastname: Wang
authors.affiliation: Huaihe Hospital, Henan University, Kaifeng, Henan 475000, P.R. China.
authors.forename: Xu-Yuan
authors.initials: XY
authors.lastname: Ma
mesh_terms: D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000235:genetics / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects*; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D045304:Cytochromes c / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D053582:Interleukin-1alpha / Q000494:pharmacology*; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism*; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D051379:Mice; D010006:Osteoblasts / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000235:genetics / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
chemical_list: D053582:Interleukin-1alpha; D047428:Protein Kinase Inhibitors; D012333:RNA, Messenger; D051028:bcl-2-Associated X Protein; D045304:Cytochromes c; D048031:JNK Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D000469:Alkaline Phosphatase; D053148:Caspase 3