{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,19]],"date-time":"2026-06-19T20:03:09Z","timestamp":1781899389930,"version":"3.54.5"},"reference-count":30,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2023,8,8]],"date-time":"2023-08-08T00:00:00Z","timestamp":1691452800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81960203"],"award-info":[{"award-number":["81960203"]}],"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":["82101032"],"award-info":[{"award-number":["82101032"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Oral Pathology Medicine"],"published-print":{"date-parts":[[2023,10]]},"abstract":"Abstract<\/jats:title>\n \n Background<\/jats:title>\n Odontogenic keratocysts (OKCs) are odontogenic jaw lesions that cause destruction and dysfunction of the jawbone. OKCs can be sporadic or associated with nevoid basic cell carcinoma syndrome (NBCCS). However, the factors that initiate OKCs and the mechanism of cyst formation remain unclear. Here, we investigated the impact of PTCH1 and SMO mutations on disease progression, as well as the effects of sonic hedgehog (SHH) signaling pathway inhibitors GDC\u20100449 and GANT61 on OKC fibroblasts.<\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n Eight sporadic OKC fibroblasts without gene mutations were used as the control, and six NBCCS\u2010related fibroblasts were cultured in vitro. The effect of PTCH1 non\u2010truncated mutation 3499G>A (p.G1167R) and SMO c.2081C>G (p.P694R) mutation on OKC fibroblast proliferation was examined by EdU assay. CCK8 and wound\u2010healing assays detected the effects of OKC fibroblasts carrying PTCH1 c.3499G>A (p.G1167R) and SMO c.2081C>G (p.P694R) mutations on the proliferation and migration of HaCaT cells after co\u2010culture. Quantitative real\u2010time PCR detected the effects of GDC\u20100449 or GANT61 on the SHH signaling pathway in NBCCS\u2010related OKCs with PTCH1 truncated mutations and PTCH1 c.3499G>A (p.G1167R) and\/or SMO c.2081C>G (p.P694R) mutations.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n PTCH1 c.3499G>A (p.G1167R) and SMO c.2081C>G (p.P694R) promoted the proliferation of OKC fibroblasts. The proliferation and migration of HaCaT cells were affected by NBCCS\u2010related OKC fibroblasts carrying PTCH1 c.3499G>A (p.G1167R) and SMO c.2081C>G (p.P694R) mutations. GDC\u20100449 significantly inhibited the SHH signaling pathway in NBCCS\u2010related OKC fibroblasts with PTCH1 truncated mutations. An NBCCS\u2010related OKC carrying PTCH1 c.3499G>A (p.G1167R) and SMO c.2081C>G (p.P694R) mutations were resistant to GDC\u20100449 but inhibited by GANT61.<\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n Genetic mutations in OKC fibroblasts may affect the biological behavior of epithelial and stromal cells and cause disease. GDC\u20100449 could be used to treat OKCs, especially NBCCS\u2010related OKCs with PTCH1 truncated mutations. SMO c.2081C>G (p.P694R) may lead to resistance to GDC\u20100449; however, GANT61 may be used as an alternative inhibitor.<\/jats:p>\n <\/jats:sec>","DOI":"10.1111\/jop.13473","type":"journal-article","created":{"date-parts":[[2023,8,8]],"date-time":"2023-08-08T13:48:13Z","timestamp":1691502493000},"page":"867-876","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["PTCH<\/scp>\n \/\n SMO<\/scp>\n gene mutations in odontogenic keratocysts and drug interventions"],"prefix":"10.1111","volume":"52","author":[{"given":"Shan","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Basic Science, School of Stomatology Kunming Medical University Kunming China"},{"name":"Yunnan Key Laboratory of Stomatology Kunming China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yingying","family":"Hong","sequence":"additional","affiliation":[{"name":"First Clinical Division Peking University School and Hospital of Stomatology & National Center of Stomatology & National Clinical Research Center for Oral Diseases & National Engineering Research Center of Oral Biomaterials and Digital Medical Devices & Beijing Key Laboratory of Digital Stomatology Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiafei","family":"Qu","sequence":"additional","affiliation":[{"name":"International VIP Dental Clinic, Tianjin Stomatological Hospital, School of Medicine Nankai University, Tianjin Key Laboratory of Oral and Maxillofacial Function Reconstruction Tianjin China"},{"name":"Tianjin Key Laboratory of Oral and Maxillofacial Function Reconstruction Tianjin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianyun","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Oral Pathology Peking University School and Hospital of Stomatology & National Center of Stomatology & National Clinical Research Center for Oral Diseases & National Engineering Laboratory for Digital and Material Technology of Stomatology & Beijing Key Laboratory of Digital Stomatology Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuhao","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Stomatology The First People's Hospital of Yunnan Province Kunming China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiemei","family":"Zhai","sequence":"additional","affiliation":[{"name":"Department of Basic Science, School of Stomatology Kunming Medical University Kunming China"},{"name":"Yunnan Key Laboratory of Stomatology Kunming China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tiejun","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Oral Pathology Peking University School and Hospital of Stomatology & National Center of Stomatology & National Clinical Research Center for Oral Diseases & National Engineering Laboratory for Digital and Material Technology of Stomatology & Beijing Key Laboratory of Digital Stomatology Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,8,8]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1186\/1750\u20101172\u20103\u201032"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0733\u20108635(18)30114\u20101"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijom.2012.02.008"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.272.5268.1668"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/jbmr.2815"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0077305"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1261877"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tips.2009.03.007"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/384129a0"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.oraloncology.2014.09.016"},{"issue":"9","key":"e_1_2_10_12_1","first-page":"1798","article-title":"Missense mutations in SMOH in sporadic basal cell carcinomas of the skin and primitive neuroectodermal tumors of the central nervous system","volume":"58","author":"Reifenberger J","year":"1998","journal-title":"Cancer Res"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.3760\/cma.j.cn112144\u201020211214\u201000547"},{"issue":"5","key":"e_1_2_10_14_1","first-page":"446","article-title":"Keratocystic odontogenic tumour: reclassification of the odontogenic keratocyst from cyst to tumour","volume":"125","author":"Madras J","year":"2008","journal-title":"Tex Dent J"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mehy.2006.04.062"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1177\/0022034510379016"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1113713"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1001\/archdermatol.2011.50"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccell.2015.02.002"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41368\u2010018\u20100034\u2010x"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms10204"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600\u20100714.1975.tb01738.x"},{"issue":"4","key":"e_1_2_10_23_1","article-title":"Investigation of interleukin\u20101 alpha and interleukin\u20106 expression and interleukin\u20101 alpha gene polymorphism in keratocystic odontogenic tumors and ameloblastomas","volume":"16","author":"Seng\u00fcven B","year":"2011","journal-title":"Med Oral Patol Oral Cir Bucal"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1177\/154405910708600215"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600\u20100714.2009.00755.x"},{"issue":"1","key":"e_1_2_10_26_1","first-page":"E57","article-title":"Basal cell nevus syndrome. Presentation of six cases and literature review","volume":"10","author":"D\u00edaz\u2010Fern\u00e1ndez JM","year":"2005","journal-title":"Med Oral Patol Oral Cir Bucal"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.otohns.2009.10.008"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1177\/154405910808700616"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.psyneuen.2007.03.017"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1111\/odi.12231"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1177\/0022034514542108"}],"container-title":["Journal of Oral Pathology & Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/jop.13473","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,6]],"date-time":"2023-10-06T13:37:36Z","timestamp":1696599456000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/jop.13473"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,8,8]]},"references-count":30,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2023,10]]}},"alternative-id":["10.1111\/jop.13473"],"URL":"https:\/\/doi.org\/10.1111\/jop.13473","archive":["Portico"],"relation":{"has-review":[{"id-type":"doi","id":"10.1111\/JOP.13473\/v2\/decision1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/JOP.13473\/v1\/review1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/JOP.13473\/v1\/decision1","asserted-by":"object"}]},"ISSN":["0904-2512","1600-0714"],"issn-type":[{"value":"0904-2512","type":"print"},{"value":"1600-0714","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,8,8]]},"assertion":[{"value":"2022-12-06","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-05-26","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-08-08","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}