Abstract
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 (p < 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, p < 0.05). Our results indicate that adhesion and migration are deregulated in OFC keratinocytes, which might contribute to OFC pathogenesis.
Highlights
Orofacial clefts (OFCs) are among the most frequent congenital anomalies with a prevalence of about 8 per 10,000 live births worldwide [1]
The keratinocytes were isolated from patients of about 1.5 years of age and are obviously microarray analyses with pooled RNA samples from palatal keratinocytes from OFC patients and not identical to the embryonic cells that took part in the fusion process
We assume that the non-OFC individuals
Summary
Orofacial clefts (OFCs) are among the most frequent congenital anomalies with a prevalence of about 8 per 10,000 live births worldwide [1]. Studies in mouse models show that clefts develop following (1) failure of palatal shelf outgrowth, (2) fusion of a palatal shelf with the tongue or mandible, (3) failure of palatal shelf elevation, (4) failure of the palatal shelves to adhere to each other and (5) persistence of the MES [4]. Differentiation, migration, adhesion and apoptosis are required for fusion of the palatal shelves. Prior to adhesion of the palatal shelves, periderm cells disappear through desquamation [6,7] and possibly through migration to the oral and nasal side of the palatal shelves [8,9] exposing the medial edge epithelium (MEE). We hypothesized that genes related to crucial cellular processes for palatogenesis, such as proliferation, migration, adhesion, differentiation and apoptosis, are deregulated in keratinocytes derived from OFC patients. Our scratch assay confirmed that migration of OFC keratinocytes was reduced in comparison with non-OFC keratinocytes
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