{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T13:29:45Z","timestamp":1787923785337,"version":"build-2784847793"},"reference-count":35,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T00:00:00Z","timestamp":1787875200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100010256","name":"Guangzhou Municipal Science and Technology Project","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100010256","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100015956","name":"Special Project for Research and Development in Key Areas of Guangdong Province","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100015956","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell Dev. Biol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Oral ulcers (OU) often present with prolonged healing, recurrent episodes, and scar formation, posing challenges for clinical management. Human periodontal ligament stem cells (hPDLSCs) have shown potential in oral tissue repair, but further research is needed to clarify their mechanism of action in OU healing. This study aims to elucidate the molecular mechanisms by which hPDLSCs promote oral ulcer healing.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Method<\/jats:title>\n                    <jats:p>\n                      To identify key regulatory genes, the OU-associated microarray dataset GSE37265 was integrated with hPDLSC genomic data for differential expression analysis. Subsequently, Weighted Gene Co-expression Network Analysis (WGCNA) was used to identify functional modules associated with OU healing.\n                      <jats:italic>In vivo<\/jats:italic>\n                      , hPDLSCs were locally administered into a rat ulcer model, and therapeutic efficacy was assessed by ulcer closure rates and histological evaluation (HE and Masson\u2019s trichrome staining). Furthermore, RNA-sequencing (RNA-seq) was performed on oral mucosal tissues to delineate the underlying molecular landscape and critical signaling pathways. The involvement of the TGF-\u03b2 signaling pathway was confirmed by real-time quantitative PCR (RT-qPCR) and Western blotting (WB) analyses.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Bioinformatics analysis identified 92 key genes in hPDLSCs-mediated treatment of OU, highlighting the central role of the TGF-\u03b21\/Smad pathway. As shown by the animal studies, hPDLSCs therapy increased the healing rate to 97% by day 8 (\n                      <jats:italic>vs<\/jats:italic>\n                      . 70% in the model). Furthermore, the therapy significantly reduced inflammatory cell infiltration and abnormal collagen deposition while promoting regular collagen arrangement. Transcriptomic and molecular experiments further showed that hPDLSCs simultaneously inhibit TGF-\u03b21\/Smad and extracellular signal-regulated kinase (ERK) signaling pathways, thereby alleviating inflammatory responses and suppressing mucosal fibrosis.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>In this study, we reveal a novel role for hPDLSCs in promoting oral ulcer healing. The findings indicate that hPDLSCs suppress inflammation and fibrosis via the TGF-\u03b21\/Smad pathway, offering a promising therapeutic strategy for OU and other fibrotic conditions.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fcell.2026.1824785","type":"journal-article","created":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T12:53:42Z","timestamp":1787921622000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Human periodontal ligament stem cells promote oral ulcer healing in rats through modulation of TGF-\u03b21\/smad signaling"],"prefix":"10.3389","volume":"14","author":[{"given":"Xiang","family":"Cai","sequence":"first","affiliation":[{"name":"State Key Laboratory of Bioactive Molecules and Druggability Assessment, Jinan University","place":["Guangzhou, China"]},{"name":"Institute of Biomedicine and Guangdong Provincial Key Laboratory of Bioengineering Medicine, Jinan 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