2-Hydroxyethyl Methacrylate Inhibits Migration of Dental Pulp Stem Cells

Abstract

Objectives Cell migration is an important step in pulpal wound healing. Although components in the resin-based dental materials are known to have adverse effects on pulp wound healing including proliferation and mineralization, their effects on cell migration have been scarcely examined. Here, we investigated effects of 2-Hydroxyethyl methacrylate (HEMA) on migration of dental pulp stem cells (DPSC) in vitro. Methods Cell viability was assessed using MTT assay, and cell migration was evaluated using wound scratch assay and transwell migration assay at non-cytotoxic doses. Western blotting was used to examine pathways associated with migration such as focal adhesion kinase (FAK), mitogen-activated protein kinase (MAPK), and glycogen synthase kinase 3 (GSK3). Results There were no drastic changes in the cell viability below 3mM HEMA. When DPSC were treated with HEMA at 0.5, 1.0, and 2.5mM, cell migration was diminished. HEMA-treated DPSC exhibited the loss of phosphorylated focal adhesion kinase (FAK) in a dose-dependent manner. The HEMA-mediated inhibition of cell migration was associated with phosphorylation of p38 but not GSK3, ERK or JNK pathways. When we inhibited the p38 signaling pathway using a p38 inhibitor, migration of DPSC was suppressed. Conclusion HEMA inhibits migration of dental pulp cells in vitro, suggesting that poor pulpal wound healing under resin-based dental materials may be due, in part, to inhibition of cell migration by HEMA.

The effects of 2‐hydroxyethyl methacrylate on matrix metalloproteinases 2 and 9 in human pulp cells and odontoblast‐like cells in vitro

“…HEMA at a dose leading to a 20% reduction in cell viability inhibited the migration of human pulp cells and that this inhibitory effect increased with the HEMA concentration, consistent with previous findings (Williams et al . ). These findings suggest that HEMA inhibits the migration and differentiation of pulp cells into the odontoblast layer in vitro .…”

“…Previous research has proven that pulp cell migration can mediate different signalling pathways and that HEMA‐mediated inhibition of this migration is associated with the phosphorylation signalling proteins focal adhesion kinase and P38 (Williams et al . ). Increased phosphorylation of extracellular signal‐regulated kinase 1/2 has also been observed in HEMA‐treated cells (Spagnuolo et al .…”

Signaling Pathways in Dental Stem Cells During Their Maintenance and Differentiation

“…Two-hydroxyethyl methacrylate (HEMA), a kind of resinbased dental materials, can inhibit the cell migration of dental pulp stem cells (DPSCs) by phosphorylation of p38 but not ERK, or JNK MAPK pathways [ 12 ]. p38 MAPK and insulin-like growth factor 1 receptor (IGF-1R) are responsible for the mitotic quiescence of DPSCs.…”

“…MAPK regulates the directional migration of cells via the phosphorylation of MAPK-activated protein kinase 2/3 (MAPKAP 2/3). Some studies have demonstrated that HEMA inhibits the migration of DPSCs at non-toxic doses, and such inhibition is associated with the p38 signaling pathway [ 12 ]. Moreover, LPS can promote the adhesion and migration of DPSCs by upregulating the expression of adhesion molecules and chemotactic factors, while inhibition of MAPK and NF-κB signifi cantly antagonizes LPS-induced adhesion and migration [ 21 ].…”

Dental Pulp Stem Cell Niche

“…2-hydroxyethyl methacrylate (HEMA), a kind of resin-based dental materials, can inhibit the migration of DPSCs by phosphorylation of p38 or JNK MAPK pathways [99]. P38 MAPK and IGF-1R are responsible for the mitotic quiescence of DPSCs.…”