title: From the Cover: Activation of NF-κB-Autophagy Axis by 2-Hydroxyethyl Methacrylate Commits Dental Mesenchymal Cells to Apoptosis.
abstract: 2-hydroxyethyl methacrylate (HEMA) is the major resin monomer that is released from incomplete polymerized dental restorative and adhesive biomaterials during dental therapy. Autophagy and apoptosis are biologically connected and the relationship between autophagy and apoptosis is complex under various circumstances. This study aimed to determine whether autophagy is activated by HEMA and further explore the function of autophagy during the HEMA-induced apoptosis of dental mesenchymal cells (DMCs). We exposed DMCs to different concentrations of HEMA. Cell viability showed a time- and concentration-dependent decrease when exposed to HEMA. We showed that HEMA exposure increased autophagic vacuoles and the expression of autophagic biomarkers (Beclin1, Atg5 and LC3). Pre-incubated with autophagy inhibitors (3-methyladenine and chloroquine) significantly prevented HEMA-induced apoptosis. Interestingly, HEMA initiated nuclear factor-κB (NF-κB) expression and nuclear translocation, whereas the NF-κB inhibitor (Bay 11-7082) markedly suppressed HEMA-induced autophagic activation and apoptosis. As is consistent with the in vitro results, HEMA treatment resulted in dental pulp tissue toxicity and activation of typical autophagic vacuoles in the tooth slice organ culture model ex vivo. In summary, we demonstrated that NF-κB signaling functioned upstream of HEMA-inducecd autophagy in DMCs and that the activation of NF-κB-autophagy axis was responsible for HEMA-induced apoptosis. Our findings provide novel insights into the mechanisms of resin monomer-mediated dental pulp damage during dental treatment, highlighting the activation of NF-κB-autophagy axis as an important mechanism of HEMA-mediated apoptosis.
authors.affiliation: State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) and Key Laboratory of Oral Biomedicine Ministry of Education, Wuhan University, Wuhan, China.
authors.forename: Jing-Jing
authors.initials: JJ
authors.lastname: Yu
authors.affiliation: State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) and Key Laboratory of Oral Biomedicine Ministry of Education, Wuhan University, Wuhan, China.
authors.forename: Ling-Xin
authors.initials: LX
authors.lastname: Zhu
authors.affiliation: State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) and Key Laboratory of Oral Biomedicine Ministry of Education, Wuhan University, Wuhan, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Zhang
authors.affiliation: State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) and Key Laboratory of Oral Biomedicine Ministry of Education, Wuhan University, Wuhan, China.
authors.forename: Shan
authors.initials: S
authors.lastname: Liu
authors.affiliation: State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) and Key Laboratory of Oral Biomedicine Ministry of Education, Wuhan University, Wuhan, China.
authors.forename: Feng-Yuan
authors.initials: FY
authors.lastname: Lv
authors.affiliation: State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) and Key Laboratory of Oral Biomedicine Ministry of Education, Wuhan University, Wuhan, China.
authors.forename: Xue
authors.initials: X
authors.lastname: Cheng
authors.affiliation: State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) and Key Laboratory of Oral Biomedicine Ministry of Education, Wuhan University, Wuhan, China.
authors.forename: Guo-Jing
authors.initials: GJ
authors.lastname: Liu
authors.affiliation: State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) and Key Laboratory of Oral Biomedicine Ministry of Education, Wuhan University, Wuhan, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Peng
mesh_terms: D000293:Adolescent; D000328:Adult; D017209:Apoptosis / Q000187:drug effects*; D001343:Autophagy / Q000187:drug effects*; D000071186:Beclin-1 / Q000378:metabolism; D002478:Cells, Cultured; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D008689:Methacrylates / Q000633:toxicity*; D016328:NF-kappa B / Q000378:metabolism; D014070:Tooth / Q000166:cytology*; D055815:Young Adult
chemical_list: C491997:BECN1 protein, human; D000071186:Beclin-1; D008689:Methacrylates; D016328:NF-kappa B; C005044:hydroxyethyl methacrylate
keywords: 2-Hydroxyethyl methacrylate; NF-κB; apoptosis; autophagy; dental mesenchymal cells; tooth slice organ