HEMA modulates the transcription of genes related to oxidative defense, inflammatory response and organization of the ECM in human oral cells.

OBJECTIVES: 2-Hydroxyethyl methacrylate (HEMA) is a widely used monomer of dental resin composite materials. Incomplete curing of resins leads to elution of HEMA, which may come in contact with different cells in oral tissues. We aimed to analyze the impact of HEMA on the transcription of genes participating in detoxification of oxidative stress, inflammatory response and organization of the extracellular matrix (ECM) using human gingival fibroblasts (HGFs) and human oral keratinocytes (OKF6/TERT2).

METHODS: Cells were grown in monolayer cultures and treated with different HEMA concentrations (0.5-10mM). H33342 and LDH assays were used to determine HEMA-caused cytotoxicity. Quantitative RT-PCR was used to analyze mRNA expression of four genes related to oxidative stress and five genes each related to inflammation and organization of the ECM.

RESULTS: HEMA caused similar concentration-dependent cytotoxicity in fibroblasts and keratinocytes. Analysis of the transcription showed that genes were regulated in both cell types after HEMA treatment. Genes related to defense against oxidative stress were transcriptionally induced, genes related to inflammation were mainly reduced and genes related to the organization of the ECM were differentially modulated.

SIGNIFICANCE: We analyzed concurrent and HEMA-dependent differential expression of 14 important genes, which have a special significance for cellular processes that are linked to redox and tissue homeostasis. The results suggest that HEMA has an impact on cellular redox-homeostasis with potential impairment of inflammatory responses and of the organization of the ECM in human gingival fibroblasts and oral keratinocytes as first target cells of eluted HEMA.