{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T16:01:22Z","timestamp":1784563282461,"version":"3.55.0"},"reference-count":29,"publisher":"SAGE Publications","issue":"8","license":[{"start":{"date-parts":[[2025,12,9]],"date-time":"2025-12-09T00:00:00Z","timestamp":1765238400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"funder":[{"name":"University at Buffalo School of Dental Medicine","award":["Faculty start up funds"],"award-info":[{"award-number":["Faculty start up funds"]}]}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["J Dent Res"],"published-print":{"date-parts":[[2026,7]]},"abstract":"<jats:p>\n                    Cell survival, differentiation, and death are tightly regulated processes that maintain tissue homeostasis. Arecoline and transforming growth factor\u2013beta (TGF-\u03b2) have been implicated as key mediators in oral submucous fibrosis (OSMF). The persistent, overactive fibroblasts in fibrotic lesions have altered metabolism and cytoskeletal changes. The present work evaluated the effects of arecoline and TGF-\u03b2 on the mitochondrial bioenergetics and phenotype of oral fibroblasts. Human oral fibroblasts were treated with arecoline, TGF-\u03b21, and combinations and evaluated for cell survival using AlamarBlue and vital staining. To assess mitochondrial fusion, MF18 inhibitor and OPA-1, MFN-2, and fission, Mdivi inhibitor and DRP-1 were used. Changes in cell responses were assessed with real-time quantitative polymerase chain reaction, immunofluorescence, and Seahorse analysis. Following institutional review board approval, archival human tissue biopsies from OSMF at various grades were evaluated for correlation with modulation of fibroblast metabolism and cytoskeletal changes. Arecoline-treated fibroblasts showed significant (\n                    <jats:italic toggle=\"yes\">n<\/jats:italic>\n                    = 3,\n                    <jats:italic toggle=\"yes\">P<\/jats:italic>\n                    &lt; 0.05) cell death rescued by TGF-\u03b21 treatments (\n                    <jats:italic toggle=\"yes\">n<\/jats:italic>\n                    = 3,\n                    <jats:italic toggle=\"yes\">P<\/jats:italic>\n                    &lt; 0.05). Further examination revealed that arecoline-treated cells exhibited mitochondrial fission with a glycolytic (reduced transcription factor of mitochondria [TFAM], increased hexokinase II,\n                    <jats:italic toggle=\"yes\">n<\/jats:italic>\n                    = 3,\n                    <jats:italic toggle=\"yes\">P<\/jats:italic>\n                    &lt; 0.05) metabolic profile and reduced OPA1 expression. In contrast, TGF-\u03b21 treatments demonstrated mitochondrial fusion, accompanied by increased OPA1 expression. Combined treatments with arecoline and TGF-\u03b21 demonstrated improved cell survival, reduced fission, and improved mitochondrial bioenergetics. These results correlated with increased TFAM and vimentin\u2013actin (VA) expression, representing a synthetic, overactive fibroblast phenotype. Finally, clinical samples from patients with OSMF exhibited a progressive increase in TFAM and VA-positive fibroblasts in advanced clinical disease, corroborating the in vitro observations. TGF-\u03b21 appears to modulate mitochondrial responses in arecoline-induced cytotoxicity, resulting in fibroblast survival, leading to a profibrotic phenotype. These observations suggest that selective targeting of the mitochondria driving these surviving myofibroblasts may serve as a novel therapeutic target for clinical translation.\n                  <\/jats:p>","DOI":"10.1177\/00220345251394281","type":"journal-article","created":{"date-parts":[[2025,12,10]],"date-time":"2025-12-10T04:20:56Z","timestamp":1765340456000},"page":"1068-1078","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":1,"title":["TGF-\u03b21 Directs TFAM-Mediated Mitochondrial Reprogramming in Oral Submucous Fibrosis"],"prefix":"10.1177","volume":"105","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3281-731X","authenticated-orcid":false,"given":"K.M.","family":"Desai","sequence":"first","affiliation":[{"name":"Oral Biology, Surgery, and Biomedical Engineering, University at Buffalo, Buffalo, NY, USA"},{"name":"Oral Pathology, KLE VK Institute of Dental Sciences, KLE Academy of Higher Education and Research (KLE University), Belagavi, Karnataka, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"N.A.","family":"Tadkalkar","sequence":"additional","affiliation":[{"name":"Electron Microscopy Group, ICMR - National Institute of Virology, Pune, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Amin","sequence":"additional","affiliation":[{"name":"Oral Biology, Surgery, and Biomedical Engineering, University at Buffalo, Buffalo, NY, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R.","family":"Kumar","sequence":"additional","affiliation":[{"name":"Roswell Park Cancer Institute, Buffalo, NY, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S.U.","family":"Rahman","sequence":"additional","affiliation":[{"name":"Oral Biology, Surgery, and Biomedical Engineering, University at Buffalo, Buffalo, NY, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S.","family":"Ponnusamy","sequence":"additional","affiliation":[{"name":"Oral Biology, Surgery, and Biomedical Engineering, University at Buffalo, Buffalo, NY, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P.","family":"Angadi","sequence":"additional","affiliation":[{"name":"Oral Pathology, KLE VK Institute of Dental Sciences, KLE Academy of Higher Education and Research (KLE University), Belagavi, Karnataka, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"W.","family":"Liu","sequence":"additional","affiliation":[{"name":"Pediatrics, Jacob School of Medicine and Biomedical Sciences, Buffalo, NY, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R.V","family":"Dayani","sequence":"additional","affiliation":[{"name":"Oral Biology, Surgery, and Biomedical Engineering, University at Buffalo, Buffalo, NY, 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