Enamel defects of Axenfeld‐Rieger syndrome and the role of PITX2 in its pathogenesis
Enamel defects of Axenfeld‐Rieger syndrome and the role of PITX2 in its pathogenesis
复制标题
Axenfeld-Rieger 综合征的牙釉质缺陷及 PITX2 在其发病机制中的作用
DOI：
10.1111/odi.14315
复制
发表时间：
2022
期刊：
影响因子：
3.8
通讯作者：
Wang Xin
中科院分区：
文献类型：
--
作者：
Yang Yi;Zhu Junxia;Chiba Yuta;Fukumoto Satoshi;Qin Man;Wang Xin
目的研究AXF-Rieger综合征(ARS)伴类同源异型域2(PITX2)杂合性微缺失所致牙体异常的超微结构特征，探讨其致牙釉质缺失的分子机制。对1例急性呼吸窘迫综合征患者剥脱的牙齿进行扫描电子显微镜和微电脑断层扫描分析。建立稳定的PITX2基因敲除细胞系以模拟PITX2单倍体缺陷。分析细胞增殖和成釉细胞分化情况，探讨Wnt/β-catenin通路在成釉细胞前体细胞增殖中的作用。结果发现PITX2基因缺失约0.216 Mb。患牙表现为牙釉质变薄、破碎，牙釉质生物矿化异常。结论Pitx2基因敲除后部分ARS患者釉质形成障碍，Pitx2基因敲除可影响内釉上皮细胞的增殖和成釉细胞分化，Pitx2可能通过Wnt/β-catenin信号通路调节细胞增殖。
ObjectivesTo investigate the detailed ultrastructural patterns of dental abnormalities affected by Axenfeld‐Rieger syndrome (ARS) with a heterozygous microdeletion involving paired‐like homeodomain 2 (PITX2) and explored the underlying molecular mechanisms driving enamel defects.Subjects and methodsSanger sequencing, genomic quantitative PCR analysis, and chromosomal microarray analysis (CMA) were used to screen the disease‐causing mutation in one ARS proband. An exfoliated tooth from an ARS patient was analyzed with scanning electron microscopy and micro–computerized tomography. A stablePitx2knockdown cell line was generated to simulatePITX2haploinsufficiency. Cell proliferation and ameloblast differentiation were analyzed, and the role of the Wnt/β‐catenin pathway in proliferation of ameloblast precursor cells was investigated.ResultsAn approximately 0.216 Mb novel deletion encompassingPITX2was 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 afterPitx2knockdown.ConclusionsEnamel formation is disturbed in some patients with ARS.Pitx2knockdown can influence the proliferation and ameloblast differentiation of inner enamel epithelial cells, and PITX2 may regulate cell proliferation via Wnt/β‐catenin signaling pathway.