Expression and Functional Importance of Discoidin Domain Receptors in Dentoalveolar Tissues

Objectives: Collagen type I is an essential extracellular matrix (ECM) structural protein in dentoalveolar tissues, including dentin and cementum, and the rapidly remodeling periodontal ligament (PDL) and alveolar bone. Discoidin domain receptors (DDR1 and DDR2) regulate collagen fibrillogenesis and deposition in the ECM, and their extracellular domains have been shown to control mineral deposition. The roles of DDRs in dentoalveolar development and function have not been previously reported. In these studies, we aimed to analyze Ddr1 and Ddr2 mRNA expression during dentoalveolar development, and test the functional importance of DDR1 using a mouse model.
Methods: We analyzed spatiotemporal expression of Ddr1 and Ddr2 in mice from 8 to 60 days postnatal (dpn) by in situ hybridization (ISH). Tissues from wild-type (WT) and Ddr1 knock-out (Ddr1^-/-) mice were harvested at 4-6 months and analyzed via radiography, microcomputed tomography, histology, and histomorphometry.
Results: Expression of Ddr1 was identified in the epithelial tissues including the enamel organ and gingiva, but expression was not detected in any ectomesenchymal cells of the pulp, dentin, or periodontium. Conversely, Ddr2 expression was identified in odontoblasts and osteoblasts. Radiography revealed no major differences in Ddr1^-/- vs. WT dentoalveolar structures; however, Ddr1^-/- mandibles featured defective condyles and abnormal subchondral bone structure. Histomorphometry measurements of oral, dental, and periodontal tissues did not identify significant anatomic differences, including gingival epithelium.
Conclusions: These studies indicate distinct expression patterns for DDR1 and DDR2, suggesting dissimilar functions in dentoalveolar tissues. While oral and dentoalveolar tissues appear functional in the absence of DDR1, ongoing studies will analyze mineralization in bones and teeth in these mice.