{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,9]],"date-time":"2026-11-09T21:59:11Z","timestamp":1794261551614,"version":"4.9.0"},"reference-count":66,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2005,6,6]],"date-time":"2005-06-06T00:00:00Z","timestamp":1118016000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J Oral Pathology Medicine"],"published-print":{"date-parts":[[2005,7]]},"abstract":"<jats:p>\n                    Oral submucous fibrosis (OSF) is a chronic debilitating disease and a premalignant condition of the oral cavity. It is characterized by a generalized submucosal fibrosis. The pathogenesis of the disease is not well established. Epidemiological evidences strongly indicate the association of the betel quid (BQ) habit and OSF. Various findings indicate the disease to be a consequence of disturbances in the homeostatic equilibrium between synthesis and degradation of extracellular matrix (ECM), wherein collagen forms a major component, thus can be considered as a collagen\u2010metabolic disorder. Transforming growth factor\u2010beta (TGF\u2010\n                    <jats:italic>\u03b2<\/jats:italic>\n                    ) is a potent stimulator of production and deposition of the ECM. The objectives of this review are to highlight the molecular events involved in the overproduction of insoluble collagen and decreased degradation of collagen occurring via exposure to BQ and stimulation of the TGF\u2010\n                    <jats:italic>\u03b2<\/jats:italic>\n                    pathway, and elucidate the cell signaling that is involved in the etiopathogenesis of the disease process.\n                  <\/jats:p>","DOI":"10.1111\/j.1600-0714.2005.00325.x","type":"journal-article","created":{"date-parts":[[2005,9,12]],"date-time":"2005-09-12T06:45:57Z","timestamp":1126507557000},"page":"321-328","source":"Crossref","is-referenced-by-count":251,"title":["Molecular pathogenesis of oral submucous fibrosis \u2013 a collagen metabolic disorder"],"prefix":"10.1111","volume":"34","author":[{"given":"P.","family":"Rajalalitha","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S.","family":"Vali","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2005,6,6]]},"reference":[{"key":"e_1_2_6_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/0030-4220(66)90367-7"},{"key":"e_1_2_6_3_2","first-page":"224","article-title":"Oral submucous fibrosis as a precancerous condition","volume":"92","author":"Pindborg JJ","year":"1984","journal-title":"Scand J Dent Res"},{"key":"e_1_2_6_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bdj.4805876"},{"key":"e_1_2_6_5_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0714.1990.tb00821.x"},{"key":"e_1_2_6_6_2","first-page":"497","article-title":"A statistical study on oral carcinomas in Taiwan with emphasis on the relationship with betel nut chewing: a preliminary report","volume":"75","author":"Kwan HW","year":"1976","journal-title":"J Formos Med Assoc"},{"key":"e_1_2_6_7_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0714.1990.tb00804.x"},{"key":"e_1_2_6_8_2","first-page":"163","article-title":"The aetiology of oral submucous fibrosis: the stimulation of collagen synthesis by extracts of areca nut","volume":"10","author":"Canniff JP","year":"1981","journal-title":"Int J Oral Surg"},{"key":"e_1_2_6_9_2","doi-asserted-by":"publisher","DOI":"10.1093\/carcin\/21.7.1365"},{"key":"e_1_2_6_10_2","doi-asserted-by":"publisher","DOI":"10.1034\/j.1600-0714.2003.00004.x"},{"key":"e_1_2_6_11_2","doi-asserted-by":"publisher","DOI":"10.1034\/j.1600-0714.2000.290304.x"},{"key":"e_1_2_6_12_2","first-page":"568","article-title":"Betel\u2010nut chewing and submucous fibrosis in Durban","volume":"74","author":"Seedat HA","year":"1998","journal-title":"S Afr Med J"},{"key":"e_1_2_6_13_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1834-7819.1996.tb03136.x"},{"key":"e_1_2_6_14_2","first-page":"646","article-title":"Interaction of collagen\u2010related genes and susceptibility to betel quid\u2010induced oral submucous fibrosis","volume":"11","author":"Chiu CJ","year":"2002","journal-title":"Cancer Epidemiol Biomarkers Prev"},{"key":"e_1_2_6_15_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0528.1997.tb00959.x"},{"key":"e_1_2_6_16_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0528.1985.tb00468.x"},{"key":"e_1_2_6_17_2","first-page":"263","article-title":"Prevention of BQ Chewers\u2019 Oral Cancer in the Asian\u2010Pacific Area Asian Pacific","volume":"2","author":"Chiba I","year":"2001","journal-title":"J Cancer Prev"},{"key":"e_1_2_6_18_2","first-page":"389","article-title":"Oral submucous fibrosis: a review with case reports","volume":"53","author":"Hardie J","year":"1987","journal-title":"J Can Dent Assoc"},{"key":"e_1_2_6_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/0003-9969(86)90112-3"},{"key":"e_1_2_6_20_2","first-page":"106","article-title":"Collagenase activity in oral submucous fibrosis","volume":"16","author":"Shieh TY","year":"1992","journal-title":"Proc Natl Sci Counc Republic China Part B Life Sci"},{"key":"e_1_2_6_21_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199411103311907"},{"key":"e_1_2_6_22_2","first-page":"465","article-title":"Enhanced expression of mRNA for transforming growth factor\u2010\u03b2, type I and type III procollagen in human post\u2010burn hypertrophic scar tissues","volume":"122","author":"Ghahary A","year":"1993","journal-title":"J Lab Clin Med"},{"key":"e_1_2_6_23_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0714.1999.tb01985.x"},{"key":"e_1_2_6_24_2","first-page":"141","article-title":"Tobacco habits other than smoking; 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