MTX treatment effects on the Notch2 ligand Jag1, Notch2, and the Notch target gene Hey1 mRNA expression and the role of Notch2 signalling in MTX-induced Hey1 induction in cultured rat bone marrow-derived endothelial cells (BMECs). Quantitative real-time PCR gene expression analyses of (A) Jag1, (B) Notch2, (C) Hey1, using RNA isolated from control and MTX-treated (10 µM for 24 h) BMECs. (D) Quantitative real time PCR for Hey1 in BMECs treated for 24 h with Saline+Control IgG, Saline+Anti-Notch2 antibody (ab), MTX+Control IgG, or with MTX+Anti-Notch2 antibody. * p < 0.05, ** p < 0.01, and **** p < 0.0001 compared to control IgG; and ### p < 0.001 compared between MTX treated groups. All results are shown as mean ± SEM from three independent experiments.

MTX treatment effects on the Notch2 ligand Jag1, Notch2, and the Notch target gene Hey1 mRNA expression and the role of Notch2 signalling in MTX-induced Hey1 induction in cultured rat bone marrow-derived endothelial cells (BMECs). Quantitative real-time PCR gene expression analyses of (A) Jag1, (B) Notch2, (C) Hey1, using RNA isolated from control and MTX-treated (10 µM for 24 h) BMECs. (D) Quantitative real time PCR for Hey1 in BMECs treated for 24 h with Saline+Control IgG, Saline+Anti-Notch2 antibody (ab), MTX+Control IgG, or with MTX+Anti-Notch2 antibody. * p < 0.05, ** p < 0.01, and **** p < 0.0001 compared to control IgG; and ### p < 0.001 compared between MTX treated groups. All results are shown as mean ± SEM from three independent experiments.

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Intensive cancer chemotherapy is well known to cause bone vasculature disfunction and damage, but the mechanism is poorly understood and there is a lack of treatment. Using a rat model of methotrexate (MTX) chemotherapy (five once-daily dosses at 0.75 mg/kg), this study investigated the roles of the Notch2 signalling pathway in MTX chemotherapy-ind...