N-acetylcysteine protects dental pulp stromal cells from HEMA-induced apoptosis by inducing differentiation of the cells.

Resin based materials are now widely used in dental restorations. While the use of these materials is aesthetically appealing in patients, they carry the risk of local and systemic adverse effects. The potential risks are direct damage to the cells and induction of immune-based hypersensitivity reactions. Dental Pulp Stromal Cells (DPSCs) and oral keratinocytes are the major cell types which may come in contact with dental resins such as 2-hydroxyethyl methacrylate (HEMA) after dental restorations. Here we show that N-acetyl cysteine (NAC) inhibits HEMA induced apoptotic cell death and restores the function of DPSCs and oral epithelial cells. NAC inhibits HEMA mediated toxicity through induction of differentiation in DPSCs since the genes for dentin sialoprotein (DSP), Osteopontin (OPN), Osteocalcin (OCN), and Alkaline Phosphatase (ALP) which are induced during differentiation are also induced by NAC. Unlike NAC, Vitamin E and C which known anti-oxidant compounds failed to prevent either HEMA mediated cell death or decrease in VEGF secretion by human DPSCs. More importantly, when added either alone or in combination with HEMA Vitamin E and Vitamin C did not increase the gene expression for OPN, and in addition Vitamin E inhibited the protective effect of NAC on DPSCs. NAC inhibited HEMA mediated decrease in NFκB activity thus, providing survival mechanism for the cells. Overall, the studies reported in this paper indicated that undifferentiated DPSCs have exquisite sensitivity to HEMA induced cell death, and their differentiation by NAC resulted in an increased NFκB activity which might have provided the basis for their increased protection from HEMA mediated functional loss and cell death.