AUTHOR=Inubushi Toshihiro , Priyanka Nag , Watanabe Masakatsu , Takahashi Yusuke , Kusano Shinnosuke , Kurosaka Hiroshi , Papagerakis Silvana , Papagerakis Petros , Hayashi Mikako , Yamashiro Takashi 

TITLE=On-demand chlorine dioxide solution enhances odontoblast differentiation through desulfation of cell surface heparan sulfate proteoglycan and subsequent activation of canonical Wnt signaling

JOURNAL=Frontiers in Cell and Developmental Biology

VOLUME=11

YEAR=2023

URL=https://www.frontiersin.org/journals/cell-and-developmental-biology/articles/10.3389/fcell.2023.1271455

DOI=10.3389/fcell.2023.1271455

ISSN=2296-634X

ABSTRACT=<p>Heparan sulfate proteoglycans (HSPGs) surround the surface of odontoblasts, and their modification affects their affinity for Wnt ligands. This study proposes applying Matching Transformation System<sup>®</sup> (MA-T), a novel chlorinated oxidant, to enhance dentinogenesis. MA-T treatment in odontoblasts decreased sulfation of HSPG and upregulated the expression of <italic>dentin sialophosphoprotein</italic> (<italic>Dspp</italic>) and <italic>Dentin Matrix Protein 1</italic> (<italic>Dmp1</italic>) via activation of canonical Wnt signaling <italic>in vitro</italic>. <italic>Ex vivo</italic> application of MA-T also enhanced dentin matrix formation in developing tooth explants. Reanalysis of a public single-cell RNA-seq dataset revealed significant Wnt activity in the odontoblast population, with enrichment for <italic>Wnt10a</italic> and <italic>Wnt6</italic>. Silencing assays showed that <italic>Wnt10a</italic> and <italic>Wnt6</italic> were redundant in inducing <italic>Dspp</italic> and <italic>Dmp1</italic> mRNA expression. These Wnt ligands’ expression was upregulated by MA-T treatment, and TCF/LEF binding sites are present in their promoters. Furthermore, the Wnt inhibitors Notum and Dkk1 were enriched in odontoblasts, and their expression was also upregulated by MA-T treatment, together suggesting autonomous maintenance of Wnt signaling in odontoblasts. This study provides evidence that MA-T activates dentinogenesis by modifying HSPG and through subsequent activation of Wnt signaling.</p>