{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T23:10:22Z","timestamp":1780614622697,"version":"3.54.1"},"reference-count":30,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2022,7,21]],"date-time":"2022-07-21T00:00:00Z","timestamp":1658361600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100005089","name":"Beijing Municipal Natural Science Foundation","doi-asserted-by":"publisher","award":["7164311"],"award-info":[{"award-number":["7164311"]}],"id":[{"id":"10.13039\/501100005089","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004826","name":"Natural Science Foundation of Beijing Municipality","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004826","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Oral Diseases"],"published-print":{"date-parts":[[2023,11]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>\n                      To investigate the detailed ultrastructural patterns of dental abnormalities affected by Axenfeld\u2010Rieger syndrome (ARS) with a heterozygous microdeletion involving paired\u2010like homeodomain 2 (\n                      <jats:italic>PITX2<\/jats:italic>\n                      ) and explored the underlying molecular mechanisms driving enamel defects.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Subjects and methods<\/jats:title>\n                    <jats:p>\n                      Sanger sequencing, genomic quantitative PCR analysis, and chromosomal microarray analysis (CMA) were used to screen the disease\u2010causing mutation in one ARS proband. An exfoliated tooth from an ARS patient was analyzed with scanning electron microscopy and micro\u2013computerized tomography. A stable\n                      <jats:italic>Pitx2<\/jats:italic>\n                      knockdown cell line was generated to simulate\n                      <jats:italic>PITX2<\/jats:italic>\n                      haploinsufficiency. Cell proliferation and ameloblast differentiation were analyzed, and the role of the Wnt\/\u03b2\u2010catenin pathway in proliferation of ameloblast precursor cells was investigated.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      An approximately 0.216\u2009Mb novel deletion encompassing\n                      <jats:italic>PITX2<\/jats:italic>\n                      was identified. The affected tooth displayed a thinner and broken layer of enamel and abnormal enamel biomineralization. PITX2 downregulation inhibited the proliferation and differentiation of inner enamel epithelial cells, and LiCl stifmulation partially reversed the proliferation ability after\n                      <jats:italic>Pitx2<\/jats:italic>\n                      knockdown.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      Enamel formation is disturbed in some patients with ARS.\n                      <jats:italic>Pitx2<\/jats:italic>\n                      knockdown can influence the proliferation and ameloblast differentiation of inner enamel epithelial cells, and PITX2 may regulate cell proliferation via Wnt\/\u03b2\u2010catenin signaling pathway.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/odi.14315","type":"journal-article","created":{"date-parts":[[2022,7,15]],"date-time":"2022-07-15T01:05:36Z","timestamp":1657847136000},"page":"3654-3664","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Enamel defects of\n                    <scp>Axenfeld\u2010Rieger<\/scp>\n                    syndrome and the role of\n                    <scp>PITX2<\/scp>\n                    in its pathogenesis"],"prefix":"10.1111","volume":"29","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0173-7306","authenticated-orcid":false,"given":"Yi","family":"Yang","sequence":"first","affiliation":[{"name":"Department of Pediatric Dentistry Peking University School and Hospital of Stomatology  Beijing 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