MTA‐induced Notch activation enhances the proliferation of human dental pulp cells by inhibiting autophagic flux

Abstract

Aim To determine the roles of autophagy and Notch signalling in mineral trioxide aggregate (MTA)-mediated proliferation and differentiation of human dental pulp cells (hDPCs). Methodology hDPCs were separated from human healthy molar teeth using collagenase I/dispase II digestion and then cultured in a-MEM medium with 15% foetal bovine serum. hDPCs were seeded in 96-well plates, and cell counting kit assays were carried out to test their viability. Real-time quantitative polymerase chain reaction (qPCR) was used to evaluate ALP, Runx2, Notch1, Hes1 and Hey1 mRNA levels. Notch1, hes1, LC3 and p62 protein levels were quantified by Western blotting. Colocalization of LC3 and Notch1 was measured by immunofluorescence. Two-tailed Student's t-tests were used for statistical analysis. Results Autophagic flux was significantly (P < 0.05) inhibited by MTA extracts, causing Notch degradation arrest. This resulted in the promotion of cell proliferation and inhibition of differentiation during the logarithmic phase of cell growth. Conclusion MTA extract promoted the proliferation of hDPCs in part by activating Notch signalling through inhibition of autophagic flux during the early stage and, thus, might potentially induce rapid restoration of injured pulps.

Mineral trioxide aggregate‐induced AMPK activation stimulates odontoblastic differentiation of human dental pulp cells

“…This is consistent with a previous study that reported that autophagy positively regulates odontoblast differentiation in an inflammatory environment (Pei et al 2016). However, the results are in contrast to reports that MTA inhibited osteoclastogenesis through inhibition of the autophagic pathway (Chen et al 2017) and that MTA extract enhanced the proliferation and blocks the differentiation by inhibiting autophagic flux during the early stage of restoration in HDPCs (Qiu et al 2017), providing that autophagy differently regulates the differentiation in various cell types and physiological conditions of cells.…”

Effect of five dental pulp capping agents on cell proliferation, viability, apoptosis and mineralization of human dental pulp cells

“…In the present study, the cytotoxicity of five pulp-capping materials was evaluated. Of note, HDPCs were treated with the exudates of these materials, a method also adopted in previous studies (15)(16)(17). Another study assessed the cytotoxicity of pulp-capping materials by directly seeding the cells onto the materials evaluating the cytotoxicity (14).…”

Higher hydration performance and bioactive response of the new endodontic bioactive cement MTA HP repair compared with ProRoot MTA white and NeoMTA plus

“…Phosphate biological fluids and blood present at the external surface during surgical procedures provides phosphate ions able to promote apatite deposition enhancing the formation of a mineralized biomimetic cement‐tissue interphase. A recent investigation using MTA extract with concentration of Ca ions of 88.9 mg L −1 and Si ions of 0.22 mg L −1 to the culture medium promotes the repair of injured pulp, potentially by accelerating proliferation and reducing the time required for hDPCs to enter into the odontoblastic differentiation stage in the clinical setting …”