{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T05:18:11Z","timestamp":1788412691637,"version":"build-2803163510"},"reference-count":40,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T00:00:00Z","timestamp":1788307200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T00:00:00Z","timestamp":1788307200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81800927"],"award-info":[{"award-number":["81800927"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82170921"],"award-info":[{"award-number":["82170921"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100012542","name":"Sichuan Provincial Science and Technology Support Program","doi-asserted-by":"publisher","award":["2025JDKP0160"],"award-info":[{"award-number":["2025JDKP0160"]}],"id":[{"id":"10.13039\/100012542","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100021171","name":"Basic and Applied Basic Research Foundation of Guangdong Province","doi-asserted-by":"publisher","award":["2024A1515030249"],"award-info":[{"award-number":["2024A1515030249"]}],"id":[{"id":"10.13039\/501100021171","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Int Endodontic J"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aim<\/jats:title>\n                    <jats:p>Pulp\u2010dentine complex repair following injury is fundamental to preserving tooth vitality and function. Despite advances in understanding reparative dentinogenesis, the molecular mechanisms orchestrating odontogenic differentiation of human dental pulp stem cells (hDPSCs) remain fragmented, lacking systematic integration across transcriptomic, proteomic and metabolomic levels. This study employs integrated multi\u2010omics approaches to identify key regulatory pathways during odontogenic differentiation and elucidate the underlying mechanisms controlling pulp\u2010dentine complex repair.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methodology<\/jats:title>\n                    <jats:p>Single\u2010cell RNA sequencing was performed on human carious and healthy pulp tissues. Temporal proteomic and metabolomic profiling was conducted during hDPSCs' odontogenic differentiation. Based on multi\u2010omics integration revealing glutathione metabolism as a central regulatory node, hDPSCs were treated with L\u2010buthionine\u2010sulfoximine (BSO) or exogenous glutathione (GSH). Intracellular reactive oxygen species (ROS), GSH levels, mitochondrial membrane potential and mitophagy markers (PINK1\/Parkin) were quantified. siRNA\u2010mediated PINK1 knockdown was performed to assess the involvement of PINK1 in GSH\u2010regulated odontogenic differentiation. A mouse molar injury model evaluated GSH effects on tertiary dentine formation in\u00a0vivo.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Single\u2010cell transcriptomic analysis revealed enrichment of oxidative stress response pathways in mesenchymal stem cells from injured pulp. Multi\u2010omics integration identified glutathione metabolism as a central regulatory pathway, with glutamate\u2010cysteine ligase catalytic subunit (GCLC) progressively upregulated during differentiation. BSO treatment depleted intracellular GSH, elevated ROS levels, suppressed PINK1\/Parkin\u2010mediated mitophagy and impaired odontogenic differentiation. GSH supplementation restored mitophagy activity and rescued differentiation capacity in\u00a0vitro. PINK1 depletion impaired odontogenic differentiation and markedly attenuated the pro\u2010differentiation effects of exogenous GSH. In\u00a0vivo, GSH administration enhanced tertiary dentine formation and activated mitophagy pathways in injured dental pulp.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Our findings establish that the GCLC\u2010mediated GSH antioxidant system orchestrates the odontogenic differentiation of dental pulp cells and pulp\u2010dentine complex repair via the PINK1\/Parkin\u2010mitophagy axis, revealing a novel metabolic\u2010oxideative signalling circuit as a potential therapeutic target for regenerative endodontics.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/iej.70240","type":"journal-article","created":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T05:02:01Z","timestamp":1788411721000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Glutathione Primes Mitochondrial Autophagy to Guide 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