Ameloblastin overexpression in HERS cells causes defects in periodontal structure

The mammalian periodontium is a unique support structure that anchors teeth in the jaw bone by providing firm attachment and resilient responsiveness to pressure. Clinical studies have shown a positive effect of enamel matrix derivatives on the prevention of ankylosis. Ameloblastin (AMBN) is one of the enamel matrix proteins and has been localized in Hertwig's Epithelial Root Sheath (HERS). Here we have generated a transgenic mouse model is which we have overexpressed ameloblastin in HERS cells using a K14 promoter. Objective: To test the effect of AMBN overexpression in HERS cells on periodontal development and mineralization. Methods: In order to compare periodontal tissues from wild-type and K14-AMBN overexpressing mice, mandibular mouse molars were fixed in formalin and prepared for histological analysis, whole-mount staining, scanning electron microscopy, and tomography using Argonne's Advanced Photon Source (APS). APS images were 3D-reconstructed in ImageJ. Results: Abnormal enamel color and structure in AMBN transgenic mice verified the success of our AMBN overexpression strategy. Whole mount stainings and histological sections documented that AMBN overexpressing transgenic mice featured increased periodontal ligament width and loss of cervical alveolar bone compared to wild-type controls. Scanning microscopy revealed a deeply fissured and rough root surface in AMBN overexpressing mice. APS tomographs documented jagged cementum and alveolar bone surfaces in transgenic mice. Root surface defects were confirmed using routine histology. Conclusion: Ameloblastin oeverexpression in transgenic mouse models resulted in enhanced periodontal ligament width, reduced alveolar bone, and altered root cementum surface structure. Funding by NIDCR grant DE18057 to XL is gratefully acknowledged.