{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T20:55:16Z","timestamp":1790628916976,"version":"4.1.0"},"reference-count":59,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2025,10,5]],"date-time":"2025-10-05T00:00:00Z","timestamp":1759622400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100012542","name":"Sichuan Provincial Science and Technology Support Program","doi-asserted-by":"publisher","award":["2024NSFSC0680"],"award-info":[{"award-number":["2024NSFSC0680"]}],"id":[{"id":"10.13039\/100012542","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Int Endodontic J"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aim<\/jats:title>\n                    <jats:p>Under certain conditions, infection\u2010induced inflammation may activate reparative processes to form a hard tissue barrier against microbial invasion. Autophagy participates in odontogenic differentiation during inflammation in\u00a0vitro, but its role in pulp repair remains unclear. This study investigated how autophagy regulated odontogenic differentiation within the inflammatory microenvironment, emphasising the regulatory role of connexin43 (Cx43) on autophagy.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methodology<\/jats:title>\n                    <jats:p>Autophagy activation was detected in inflamed pulpal tissues using immunofluorescence (IF). Human dental pulp cells (hDPCs) were stimulated with 0.1\/5\u2009\u03bcg\/mL lipopolysaccharide (LPS). Autophagy dynamics, including autophagic flux, were analysed through western blotting (WB), transmission electron microscopy (TEM), and mRFP\u2010GFP\u2010LC3 plasmid transfection. Odontogenic differentiation and mineralisation were assessed using molecular assays and Alizarin Red staining. Pharmacological inhibitors or activators were applied to determine autophagy's role. Cx43 knockdown in hDPCs and a dentine injury model in Cx43 cKO mice were used to validate their effects on autophagy. Results were analysed by two\u2010way ANOVA.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Autophagy\u2010related proteins were predominantly localised in the odontoblast layer. As dental pulp infection advanced, concurrent upregulation of LC3 and p62 levels was observed, indicating that autophagy activation occurs in the pulp alongside potential impairment of autophagic flux. 0.1\u2009\u03bcg\/mL LPS promoted autophagic flux, thereby facilitating odontogenic differentiation and mineralisation, whereas autophagy inhibition attenuated these effects. Conversely, 5\u2009\u03bcg\/mL LPS induced autophagosome accumulation but blocked autophagic flux, suppressing odontogenic differentiation and mineralisation; however, restoring autophagic flux reversed this inhibition. These data suggested that maintenance of autophagic flux integrity is essential for sustaining odontogenic differentiation capacity under inflammatory stress. Cx43 knockdown under high\u2010inflammatory conditions rescued autophagic flux and improved differentiation. Similarly, in the dentine injury model of cKO mice, Cx43 deletion attenuated p62 expression while upregulating DSPP expression, accompanied by enhanced tertiary dentine formation beneath the injury site, indicating that blockade of Cx43 promotes autophagic flux to improve pulp repair.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Autophagy regulates both inflammatory responses and repair processes in dental pulp. Specifically, maintaining functional autophagic flux ensures cells adapt to pathological stress while retaining their ability to form mineralised tissue. Cx43 inhibition promotes pulp repair through restoration of autophagic flux under inflammatory conditions, highlighting its potential as a therapeutic target for deep caries by synergistically modulating inflammation and promoting regeneration.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/iej.70044","type":"journal-article","created":{"date-parts":[[2025,10,6]],"date-time":"2025-10-06T04:46:51Z","timestamp":1759726011000},"page":"134-152","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["From Cells to Animals: Connexin43 Suppression Enhances Autophagic Flux to Restore Odontogenesis in Inflamed Dental Pulp"],"prefix":"10.1111","volume":"59","author":[{"given":"Peiling","family":"Hu","sequence":"first","affiliation":[{"name":"Department of Operative Dentistry and Endodontics, School of Stomatology Southwest Medical University  Luzhou 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