Department of Dentistry, Section Orthodontics and Craniofacial Biology, Radboud Institute for Molecular Life Sciences (RIMLS), Radboud University Medical Center, P.O. Box 9101, 6500 HB Nijmegen, The Netherlands.
Department of Human Genetics, KU Leuven, 3000 Leuven, Belgium.
Genes (Basel). 2019 Oct 23;10(11):836. doi: 10.3390/genes10110836.
Orofacial clefts (OFCs) are the most frequent craniofacial birth defects. An orofacial cleft (OFC) occurs as a result of deviations in palatogenesis. Cell proliferation, differentiation, adhesion, migration and apoptosis are crucial in palatogenesis. We hypothesized that deregulation of these processes in oral keratinocytes contributes to OFC. We performed microarray expression analysis on palatal keratinocytes from OFC and non-OFC individuals. Principal component analysis showed a clear difference in gene expression with 24% and 17% for the first and second component, respectively. In OFC cells, 228 genes were differentially expressed ( < 0.001). Gene ontology analysis showed enrichment of genes involved in β1 integrin-mediated adhesion and migration, as well as in P-cadherin expression. A scratch assay demonstrated reduced migration of OFC keratinocytes (343.6 ± 29.62 μm) vs. non-OFC keratinocytes (503.4 ± 41.81 μm, < 0.05). Our results indicate that adhesion and migration are deregulated in OFC keratinocytes, which might contribute to OFC pathogenesis.
口腔面裂(OFC)是最常见的颅面出生缺陷。口腔面裂是由于腭发生的偏差而产生的。细胞增殖、分化、黏附、迁移和凋亡在腭发生中至关重要。我们假设口腔角质细胞中这些过程的失调导致 OFC。我们对来自 OFC 和非-OFC 个体的腭角质细胞进行了微阵列表达分析。主成分分析显示基因表达有明显差异,第一和第二成分分别为 24%和 17%。在 OFC 细胞中,有 228 个基因差异表达(<0.001)。基因本体分析显示,参与β1 整联蛋白介导的黏附和迁移以及 P-钙黏蛋白表达的基因富集。划痕实验表明 OFC 角质细胞(343.6±29.62μm)的迁移减少,而非-OFC 角质细胞(503.4±41.81μm,<0.05)。我们的结果表明,OFC 角质细胞中的黏附和迁移受到了调节,这可能导致 OFC 的发病机制。