The dental monomer HEMA causes proteome changes in human THP‐1 monocytes

Abstract

Resin‐based biomaterials are widely used in medical and dental treatment, and both clinicians and patients are exposed to the materials. The knowledge of toxicity is mainly based on in vitro studies at exposure concentrations that induce cell death. However, severe cell damage and cell death signaling may overshadow essential cellular events caused by a possible toxicant. For dental resins, the knowledge of interaction with living cells at more clinical relevant exposure doses is sparse. 2‐Hydroxyethylmethacrylate (HEMA) is a commonly used monomer in dental resins. Measuring cellular adaptation to HEMA at concentrations that did not reduce cell viability was the main focus of this study. Stable isotope labeling with amino acids in cell culture was used to measure proteome changes in cultured THP‐1 cells exposed to HEMA. Western blotting verified the results. Cells exposed to HEMA increased their level of several cytoprotective proteins. The observed adaptation is compatible with increased oxidative burden caused by GSH depletion and the electrophilic characteristic of HEMA. The present approach to analyzing the toxic potential of HEMA yielded information on interactions with living cells is not previously reported. This detailed information is of great value to make better predictions of possible side effects in the clinic. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 107A: 851–859, 2019.

Biological aspects of modern dental composites

“…Two other studies using the ‘adaption approach’ suggest similar effects by analyzing alterations on the cellular proteome after methacrylate exposure. In addition to an increased level of proteins related to antioxidant function, increased HSP70 and p62 protein levels were seen in human monocytes after exposure to TEGDMA [ 46 ] and HEMA [ 47 ]. In the HEMA-exposed cells, the findings also pointed towards an interaction with the NFkB signaling pathway and reduced capacity for pyroptotic cell death.…”

Digital manufacturing techniques and the in vitro biocompatibility of acrylic-based occlusal device materials

“…To further assess possible cytotoxic responses, protein expression analysis was performed by standard Western blot immunoassay. Based on previous studies of HEMA-exposed cells [ 26 , 55 ], five proteins (HO-1, Pirin, NQO-1, p62, and GCLC) were chosen. The proteins are vastly associated with cellular stress response and an up-regulation of the proteins can be interpreted as increased demand for cytoprotection.…”

“…However, experiments using specimens post-cured with AF depicted a higher trend in the upregulation of the proteins compared to those post-cured with OF. This may support a higher DC in the materials post-cured with OF as upregulation of the proteins can be linked to increased release of electrophilic monomers [ 55 ]. Exposure to electrophilic monomers have previously been shown to cause GSH depletion and increased levels of oxidative stress [ 56 ].…”

“…Also, the cells exposed to Dental LT Clear (STL) extract showed upregulation of the cytoprotective proteins in a concentration-dependent manner, although not as prominent as the DLP workflow. Samuelsen et al [ 55 ] observed an upregulation of Pirin in THP-1 cells exposed to 2 mM HEMA. In our study, we could not see any changes in Pirin levels regarding the print workflows.…”

Methacrylate perspective in current dental practice

“…Diagnosis is at times hampered as the immunological response is usually delayed which may make difficult to identify the original causative material. 48.59 In addition, HEMA has been found to be toxic with human cell lines 60‐63 and HEMA mutagenicity potential concerns have been voiced 64‐67 …”