| Autor: |
Suttorp CM; Department of Orthodontics and Craniofacial Biology, Radboud University Medical Centre, Nijmegen, Netherlands.; Radboud Institute for Molecular Life Sciences, Radboud University Medical Centre, Nijmegen, Netherlands., Cremers NA; Department of Orthodontics and Craniofacial Biology, Radboud University Medical Centre, Nijmegen, Netherlands.; Radboud Institute for Molecular Life Sciences, Radboud University Medical Centre, Nijmegen, Netherlands.; Department of Rheumatology, Radboud University Medical Centre, Nijmegen, Netherlands., van Rheden R; Department of Orthodontics and Craniofacial Biology, Radboud University Medical Centre, Nijmegen, Netherlands., Regan RF; Department of Emergency Medicine, Thomas Jefferson University, Philadelphia, PA, United States., Helmich P; Department of Orthodontics and Craniofacial Biology, Radboud University Medical Centre, Nijmegen, Netherlands., van Kempen S; Department of Orthodontics and Craniofacial Biology, Radboud University Medical Centre, Nijmegen, Netherlands., Kuijpers-Jagtman AM; Department of Orthodontics and Craniofacial Biology, Radboud University Medical Centre, Nijmegen, Netherlands., Wagener FADTG; Department of Orthodontics and Craniofacial Biology, Radboud University Medical Centre, Nijmegen, Netherlands.; Radboud Institute for Molecular Life Sciences, Radboud University Medical Centre, Nijmegen, Netherlands. |
| Abstrakt: |
Disintegration of the midline epithelial seam (MES) is crucial for palatal fusion, and failure results in cleft palate. Palatal fusion and wound repair share many common signaling pathways related to epithelial-mesenchymal cross-talk. We postulate that chemokine CXCL11, its receptor CXCR3, and the cytoprotective enzyme heme oxygenase (HO), which are crucial during wound repair, also play a decisive role in MES disintegration. Fetal growth restriction and craniofacial abnormalities were present in HO-2 knockout (KO) mice without effects on palatal fusion. CXCL11 and CXCR3 were highly expressed in the disintegrating MES in both wild-type and HO-2 KO animals. Multiple apoptotic DNA fragments were present within the disintegrating MES and phagocytized by recruited CXCR3-positive wt and HO-2 KO macrophages. Macrophages located near the MES were HO-1-positive, and more HO-1-positive cells were present in HO-2 KO mice compared to wild-type. This study of embryonic and palatal development provided evidence that supports the hypothesis that the MES itself plays a prominent role in palatal fusion by orchestrating epithelial apoptosis and macrophage recruitment via CXCL11-CXCR3 signaling. |
