Dysregulation of Notch signaling related genes in oral lichen planus

Objective: To investigate a dysregulation of Notch signaling in oral lichen planus (OLP) using public available microarray dataset. Methods: A mRNA expression profiling dataset from Gene Expression Omnibus was downloaded. Differential gene expression between OLP and normal oral epithelium was examined using NetworkAnalyst. The dysregulated genes related to Notch signaling were identified. Results: Thirteen genes in Notch signaling pathway were significantly differential expressed between OLP and normal epithelium. OLP samples significantly increased the mRNA levels of HEYL, APH1B, CNTN1 and PSEN2. Whilst, ITCH, HES1, TLE2, DLK2, DTX2, NOTCH3, JAG2, RFNG, and SPEN were downregulated in OLP groups. Conclusions: Notch signaling was dysregulated and may participate in pathophysiologic process in OLP.

Regulation of osteoprotegerin expression by Notch signaling in human oral squamous cell carcinoma cell line

Objective: To investigate the influence of Notch signaling on osteoprotegerin (OPG) expression in a human oral squamous cell carcinoma cell line. Methods: Activation of Notch signaling was performed by seeding cells on Jagged1 immobilized surfaces. In other experiments, a γ-secretase inhibitor was added to the culture medium to inhibit intracellular Notch signaling. OPG mRNA and protein were determined by real-time PCR and ELISA, respectively. Finally, publicly available microarray database analysis was performed using connection up- or down-regulation expression analysis of microarrays software. Results: Jagged1-treatment of HSC-4 cells enhanced HES1 and HEY1 mRNA expres-sion, confirming the intracellular activation of Notch signaling. OPG mRNA and protein levels were significantly suppressed upon Jagged1 treatment. Correspondingly, HSC-4 cells treated with a γ-secretase inhibitor resulted in a significant reduction of HES1 and HEY1 mRNA levels, and a marked increase in OPG protein expression was observed. These results implied that Notch signaling regulated OPG expression in HSC-4 cells. However, Jagged1 did not alter OPG expression in another human oral squamous cell carcinoma cell line (HSC-5) or a human head and neck squamous cell carcinoma cell line (HN22). Conclusions: Notch signaling regulated OPG expression in an HSC-4 cell line and this mechanism could be cell line specific.