{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T16:43:35Z","timestamp":1787071415546,"version":"build-2736575974"},"reference-count":39,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"2","content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2019,5]]},"abstract":"<jats:p>Oral Submucous Fibrosis (OSMF) is a chronic progressive scarring oral disease predominantly affecting people of South Asian origin. It is characterized by juxtaepithelial inflammatory cell infiltration followed by fibrosis in the lamina propria and submucosa of the oral mucosa. The pathogenesis of the disease is not well established and a number of mechanisms have been proposed regarding the pathogenesis. A renewed interest has been shown in myofibrobasts which have been implicated to play a significant role in the pathogenesis of OSMF. The myofibroblast were initially identified by means of electron microscopy in granulation tissue of healing wounds as a modulated fibroblast exhibiting features of smooth muscle cells, with prominent bundles of microfilaments, dense bodies scattered in between, and gap junctions. The presence of myofibroblasts has successively been described in practically all fibrotic situations characterized by tissue retraction and remodeling. This review paper is an attempt to identify all the studies involving myofibroblasts and explaining the pathogenesis in a simplified manner.<\/jats:p>","DOI":"10.4103\/jomfp.jomfp_238_18","type":"journal-article","created":{"date-parts":[[2019,8,28]],"date-time":"2019-08-28T08:27:16Z","timestamp":1566980836000},"page":"257-266","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":18,"title":["The role of myofibroblasts in the progression of oral submucous fibrosis: A systematic review"],"prefix":"10.4103","volume":"23","author":[{"given":"Vijay","family":"Wadhwan","sequence":"first","affiliation":[{"name":"Department of Oral and Maxillofacial Pathology and Oral Microbiology, Subharti Dental College, Swami Vivekanand Subharti University, Meerut, Uttar Pradesh, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arvind","family":"Venkatesh","sequence":"additional","affiliation":[{"name":"Department of Oral and Maxillofacial Pathology and Oral Microbiology, Smile Square Multispecialty Dental Centre, Karur, Tamil Nadu, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vandana","family":"Reddy","sequence":"additional","affiliation":[{"name":"Department of Oral and Maxillofacial Pathology and Oral Microbiology, Subharti Dental College, Swami Vivekanand Subharti University, Meerut, Uttar Pradesh, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sangeeta","family":"Malik","sequence":"additional","affiliation":[{"name":"Department of Oral Medicine and Radiology, Subharti Dental College, Swami Vivekanand Subharti University, Meerut, Uttar Pradesh, India"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"R1-20250922","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1111\/j.1600-0714.1995.tb01156.x","article-title":"Etiology of oral submucous fibrosis with special reference to the role of areca nut chewing","volume":"24","author":"Murti","year":"1995","journal-title":"J Oral Pathol Med"},{"key":"R2-20250922","doi-asserted-by":"crossref","first-page":"182","DOI":"10.1111\/j.1600-0714.1990.tb00821.x","article-title":"Collagen in submucous fibrosis: An electron-microscopic study","volume":"19","author":"van Wyk","year":"1990","journal-title":"J Oral Pathol Med"},{"key":"R3-20250922","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1034\/j.1600-0714.2002.00117.x","article-title":"High incidence of autoantibodies in Taiwanese patients with oral submucous fibrosis","volume":"31","author":"Chiang","year":"2002","journal-title":"J Oral Pathol Med"},{"key":"R4-20250922","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1111\/j.1600-0714.2007.00579.x","article-title":"Natural history of potentially malignant oral lesions and conditions: An overview of the literature","volume":"37","author":"Napier","year":"2008","journal-title":"J Oral Pathol Med"},{"key":"R5-20250922","doi-asserted-by":"crossref","first-page":"340","DOI":"10.1111\/j.1600-0528.1985.tb00468.x","article-title":"Malignant transformation rate in oral submucous fibrosis over a 17-year period","volume":"13","author":"Murti","year":"1985","journal-title":"Community Dent Oral Epidemiol"},{"key":"R6-20250922","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1111\/j.1600-0714.2010.00999.x","article-title":"Significance of myofibroblasts in oral squamous cell carcinoma","volume":"40","author":"Thode","year":"2011","journal-title":"J Oral Pathol Med"},{"key":"R7-20250922","doi-asserted-by":"crossref","first-page":"1657","DOI":"10.1016\/j.yexcr.2013.03.015","article-title":"Triggering the landslide: The tumor-promotional effects of myofibroblasts","volume":"319","author":"Mehner","year":"2013","journal-title":"Exp Cell Res"},{"key":"R8-20250922","doi-asserted-by":"crossref","first-page":"548","DOI":"10.1126\/science.173.3996.548","article-title":"Contraction of granulation tissue in vitro: Similarity to smooth muscle","volume":"173","author":"Majno","year":"1971","journal-title":"Science"},{"key":"R9-20250922","doi-asserted-by":"crossref","first-page":"208","DOI":"10.1111\/j.1600-0714.2010.00995.x","article-title":"Evaluation of myofibroblasts in oral submucous fibrosis: Correlation with disease severity","volume":"40","author":"Angadi","year":"2011","journal-title":"J Oral Pathol Med"},{"key":"R10-20250922","first-page":"271","article-title":"Myofibroblasts: Paracrine cells important in health and disease","volume":"111","author":"Powell","year":"2000","journal-title":"Trans Am Clin Climatol Assoc"},{"key":"R11-20250922","doi-asserted-by":"crossref","first-page":"549","DOI":"10.1007\/BF02147594","article-title":"Presence of modified fibroblasts in granulation tissue and their possible role in wound contraction","volume":"27","author":"Gabbiani","year":"1971","journal-title":"Experientia"},{"key":"R12-20250922","doi-asserted-by":"crossref","first-page":"1689","DOI":"10.1097\/01.LAB.0000101911.53973.90","article-title":"Normal and pathologic soft tissue remodeling: Role of the myofibroblast, with special emphasis on liver and kidney fibrosis","volume":"83","author":"Desmouli\u00e8re","year":"2003","journal-title":"Lab Invest"},{"key":"R13-20250922","doi-asserted-by":"crossref","first-page":"561","DOI":"10.1083\/jcb.76.3.561","article-title":"Cytoplasmic filaments and gap junctions in epithelial cells and myofibroblasts during wound healing","volume":"76","author":"Gabbiani","year":"1978","journal-title":"J Cell Biol"},{"key":"R14-20250922","doi-asserted-by":"crossref","first-page":"2650","DOI":"10.1172\/JCI1876","article-title":"Regulation of proliferation of human colonic subepithelial myofibroblasts by mediators important in intestinal inflammation","volume":"101","author":"Jobson","year":"1998","journal-title":"J Clin Invest"},{"key":"R15-20250922","doi-asserted-by":"crossref","first-page":"R1113","DOI":"10.1186\/ar1790","article-title":"Shared expression of phenotypic markers in systemic sclerosis indicates a convergence of pericytes and fibroblasts to a myofibroblast lineage in fibrosis","volume":"7","author":"Rajkumar","year":"2005","journal-title":"Arthritis Res Ther"},{"key":"R16-20250922","doi-asserted-by":"crossref","first-page":"7556","DOI":"10.4049\/jimmunol.166.12.7556","article-title":"Peripheral blood fibrocytes: Differentiation pathway and migration to wound sites","volume":"166","author":"Abe","year":"2001","journal-title":"J Immunol"},{"key":"R17-20250922","doi-asserted-by":"crossref","first-page":"9343","DOI":"10.3748\/wjg.v19.i48.9343","article-title":"Smoothelin, a new marker to determine the origin of liver fibrogenic cells","volume":"19","author":"Lepreux","year":"2013","journal-title":"World J Gastroenterol"},{"key":"R18-20250922","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1016\/j.bbrc.2013.05.125","article-title":"Human xylosyltransferase-I \u2013 A new marker for myofibroblast differentiation in skin fibrosis","volume":"436","author":"Faust","year":"2013","journal-title":"Biochem Biophys Res Commun"},{"key":"R19-20250922","doi-asserted-by":"crossref","first-page":"526","DOI":"10.1038\/sj.jid.5700613","article-title":"Formation and function of the myofibroblast during tissue repair","volume":"127","author":"Hinz","year":"2007","journal-title":"J Invest Dermatol"},{"key":"R20-20250922","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1016\/j.mehy.2012.11.038","article-title":"Dietary copper: A novel predisposing factor for oral submucous fibrosis?","volume":"80","author":"Arakeri","year":"2013","journal-title":"Med Hypotheses"},{"key":"R21-20250922","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1016\/0165-4608(90)90047-E","article-title":"Sister chromatid exchanges in patients with oral submucous fibrosis","volume":"44","author":"Ghosh","year":"1990","journal-title":"Cancer Genet Cytogenet"},{"key":"R22-20250922","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1186\/1746-160X-2-33","article-title":"Circulating immune complexes and trace elements (Copper, Iron and Selenium) as markers in oral precancer and cancer: A randomised, controlled clinical trial","volume":"2","author":"Khanna","year":"2006","journal-title":"Head Face Med"},{"key":"R23-20250922","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1016\/j.cca.2007.04.014","article-title":"The role of epithelial-mesenchymal transition in oral squamous cell carcinoma and oral submucous fibrosis","volume":"383","author":"Yanjia","year":"2007","journal-title":"Clin Chim Acta"},{"key":"R24-20250922","doi-asserted-by":"crossref","first-page":"940","DOI":"10.1016\/j.oraloncology.2005.05.006","article-title":"The upregulation of insulin-like growth factor-1 in oral submucous fibrosis","volume":"41","author":"Tsai","year":"2005","journal-title":"Oral Oncol"},{"key":"R25-20250922","doi-asserted-by":"crossref","first-page":"557","DOI":"10.1016\/j.oraloncology.2006.06.007","article-title":"Elevated expression of NF-kappaB in oral submucous fibrosis \u2013 Evidence for NF-kappaB induction by safrole in human buccal mucosal fibroblasts","volume":"43","author":"Ni","year":"2007","journal-title":"Oral Oncol"},{"key":"R26-20250922","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1016\/S1368-8375(01)00083-5","article-title":"Elevated vimentin expression in buccal mucosal fibroblasts by arecoline in vitro as a possible pathogenesis for oral submucous fibrosis","volume":"38","author":"Chang","year":"2002","journal-title":"Oral Oncol"},{"key":"R27-20250922","doi-asserted-by":"crossref","first-page":"366","DOI":"10.1002\/path.2786","article-title":"Betel-derived alkaloid up-regulates keratinocyte alphavbeta6 integrin expression and promotes oral submucous fibrosis","volume":"223","author":"Moutasim","year":"2011","journal-title":"J Pathol"},{"key":"R28-20250922","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1111\/odi.12151","article-title":"Clinical significance of aberrant vimentin expression in oral premalignant lesions and carcinomas","volume":"20","author":"Sawant","year":"2014","journal-title":"Oral Dis"},{"key":"R29-20250922","doi-asserted-by":"crossref","first-page":"549041","DOI":"10.1155\/2013\/549041","article-title":"Immunohistochemical analysis of vimentin in oral submucous fibrosis","volume":"2013","author":"Nayak","year":"2013","journal-title":"J Cancer Epidemiol"},{"key":"R30-20250922","doi-asserted-by":"crossref","first-page":"e55122","DOI":"10.1371\/journal.pone.0055122","article-title":"Elevation of S100A4 expression in buccal mucosal fibroblasts by arecoline: Involvement in the pathogenesis of oral submucous fibrosis","volume":"8","author":"Yu","year":"2013","journal-title":"PLoS One"},{"key":"R31-20250922","first-page":"ZC14","article-title":"Evaluation of myofibroblasts by expression of alpha smooth muscle actin: A marker in fibrosis, dysplasia and carcinoma","volume":"8","author":"Rao","year":"2014","journal-title":"J Clin Diagn Res"},{"key":"R32-20250922","doi-asserted-by":"crossref","first-page":"698","DOI":"10.1111\/jcmm.12219","article-title":"Arecoline-induced myofibroblast transdifferentiation from human buccal mucosal fibroblasts is mediated by ZEB1","volume":"18","author":"Chang","year":"2014","journal-title":"J Cell Mol Med"},{"key":"R33-20250922","doi-asserted-by":"crossref","first-page":"243","DOI":"10.4103\/0976-433X.145126","article-title":"Immunohistochemical evaluation of myofibroblasts using alpha-smooth muscle actin in oral submucous fibrosis","volume":"5","author":"Philip","year":"2014","journal-title":"SRM J Res Dent Sci"},{"key":"R34-20250922","doi-asserted-by":"crossref","first-page":"87","DOI":"10.4103\/0019-509X.175580","article-title":"Stromal myofibroblasts in oral squamous cell carcinoma and potentially malignant disorders","volume":"52","author":"Jayaraj","year":"2015","journal-title":"Indian J Cancer"},{"key":"R35-20250922","article-title":"Elevation of Twist expression by arecoline contributes to the pathogenesis of oral submucous fibrosis","author":"Lee","year":"2015","journal-title":"J Formos Med Assoc"},{"key":"R36-20250922","doi-asserted-by":"crossref","first-page":"893","DOI":"10.4103\/0973-1482.147700","article-title":"Evaluation of stromal myofibroblasts in oral leukoplakia, oral submucous fibrosis, and oral squamous cell carcinoma \u2013 An immunohistochemical study","volume":"11","author":"Gupta","year":"2015","journal-title":"J Cancer Res Ther"},{"key":"R37-20250922","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1016\/S1359-6101(99)00010-6","article-title":"Latent transforming growth factor-beta binding proteins (LTBPs) \u2013 Structural extracellular matrix proteins for targeting TGF-beta action","volume":"10","author":"Saharinen","year":"1999","journal-title":"Cytokine Growth Factor Rev"},{"key":"R38-20250922","doi-asserted-by":"crossref","first-page":"392","DOI":"10.1038\/nrc1877","article-title":"Fibroblasts in cancer","volume":"6","author":"Kalluri","year":"2006","journal-title":"Nat Rev Cancer"},{"key":"R39-20250922","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1111\/j.1600-0714.1994.tb00259.x","article-title":"Mutations of Ki-ras oncogene codon 12 in betel quid chewing-related human oral squamous cell carcinoma in Taiwan","volume":"23","author":"Kuo","year":"1994","journal-title":"J Oral Pathol Med"}],"container-title":["Journal of Oral and Maxillofacial Pathology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ovid.com\/01233803-201923020-00019","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T15:45:48Z","timestamp":1787067948000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ovid.com\/01233803-201923020-00019"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,5]]},"references-count":39,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2019]]}},"URL":"https:\/\/doi.org\/10.4103\/jomfp.jomfp_238_18","relation":{},"ISSN":["0973-029X","1998-393X"],"issn-type":[{"value":"0973-029X","type":"print"},{"value":"1998-393X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,5]]},"assertion":[{"value":"2018-09-21","name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-05-13","name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}}]}}