{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T15:22:53Z","timestamp":1790868173959,"version":"4.1.0"},"reference-count":35,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,1,16]],"date-time":"2026-01-16T00:00:00Z","timestamp":1768521600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["NRF-2022R1I1A2063745"],"award-info":[{"award-number":["NRF-2022R1I1A2063745"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["RS-2023-00252263)"],"award-info":[{"award-number":["RS-2023-00252263)"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Physiol."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>\n                      O-GlcNAcylation, a reversible post-translational modification regulated by O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA), is involved in various cellular processes, such as proliferation, differentiation, and inflammation modulation. Developmental study revealed that proper O-GlcNAcylation mediated by OGT is vital for tooth morphogenesis. However, the function of O-GlcNAcylation during reparative dentin formation is still unknown. To understand its therapeutic relevance in regenerative dentistry, we examined the potential of OGA inhibitor, Thiamet-G, in reparative dentin formation using both\n                      <jats:italic>in vitro<\/jats:italic>\n                      and\n                      <jats:italic>in vivo<\/jats:italic>\n                      approaches.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Human dental pulp stem cells were cultivated to examine cell viability, alkaline phosphatase (ALP) activity, and mRNA expression of reparative dentin-related genes. Furthermore, the dental pulp of the upper first molar in 8-week-old male ICR mice was exposed, and Thiamet-G was locally delivered for\n                      <jats:italic>in vivo<\/jats:italic>\n                      studies. Histological and immunohistochemical alterations were analyzed after 3 and 5 days post-cavity preparation, and dentin-bridge formation was evaluated at 42 days using histology and micro-CT.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      <jats:italic>In vitro,<\/jats:italic>\n                      Thiamet-G treatment facilitated proliferation, ALP activity, and upregulated expression of reparative dentin-related genes, including BMP2, BSP, DSPP, OCN, and RUNX2.\n                      <jats:italic>In vivo,<\/jats:italic>\n                      Thiamet-G treated specimens showed the altered localizations of NESTIN, NF-\u03baB, MPO, OPN, RUNX2, TGF-\u03b21, and TNF-\u03b1 at 3 and 5 days post exposure, suggesting enhanced dentin regeneration and modulated inflammation. Particularly, at 42 days, Thiamet-G treated specimens exhibited enhanced dentin-bridge formation, confirmed by micro-CT imaging and histology.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Thiamet-G treatment facilitated reparative dentin formation by modulating inflammation and regulating regenerating signaling, suggesting its potential as a therapeutic agent.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fphys.2025.1739168","type":"journal-article","created":{"date-parts":[[2026,1,16]],"date-time":"2026-01-16T05:22:12Z","timestamp":1768540932000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":3,"title":["Thiamet-G facilitates reparative dentin formation via modulating O-GlcNAcylation and inflammation"],"prefix":"10.3389","volume":"16","author":[{"given":"Elina","family":"Pokharel","sequence":"first","affiliation":[{"name":"Department of Biochemistry, School of Dentistry, IHBR, Kyungpook National University","place":["Daegu, Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tae-Young","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, School of Dentistry, IHBR, Kyungpook National University","place":["Daegu, Republic of Korea"]},{"name":"Department of Anatomy, Keimyung University School of Medicine","place":["Daegu, Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bandana","family":"Rana","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, School of Dentistry, IHBR, Kyungpook National University","place":["Daegu, Republic of 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Kyungpook National University School of Dentistry, IHBR, ITRD","place":["Daegu, Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hitoshi","family":"Yamamoto","sequence":"additional","affiliation":[{"name":"Department of Histology and Developmental Biology, Tokyo Dental College","place":["Tokyo, Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mee-Seon","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Pathology, School of Dentistry, Kyungpook National University, Kyungpook National University Hospital","place":["Daegu, Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wern-Joo","family":"Sohn","sequence":"additional","affiliation":[{"name":"College of K-Biohealth, Daegu Haany University","place":["Gyeongsan, Republic of 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