Expression and Functional Importance of Discoidin Domain Receptor 1 in Dentoalveolar Tissues
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Publisher:The Ohio State University
Series/Report no.:The Ohio State University. Department of Biomedical Engineering Undergraduate Research Theses; 2017
Collagen fibrils are abundant in all parts of the body and function to strengthen and support the extracellular framework in animal tissue. Collagen is a main component of fascia, cartilage, ligaments, tendons, bones and teeth. Like other connective tissues in the body, dentoalveolar tissues, including gingiva, dentin, cementum, periodontal ligament (PDL), and alveolar bone, are composed primarily of type I collagen as the major protein component. Discoidin domain receptors (DDR1 and DDR2) are receptors for several collagen types. They have been found to regulate collagen fibrillization and deposition in extracellular matrix (ECM) remodeling via tyrosine kinase activity, thereby modulating cell proliferation and affecting development of tissues. There have been limited studies on the expression and function of DDR1 during dentoalveolar development. In this study, we defined the expression patterns of DDR1 in dentoalveolar tissues and investigated the functional importance of DDR1 in tooth development using a DDR1-deficient mouse model. 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. These studies indicate distinct expression patterns for DDR1 and DDR2, suggesting dissimilar functions in dentoalveolar tissues. Our findings indicate signs of osteoarthritis in the DDR1-deficient condylar process and periodontitis in the 2nd and 3rd molars of the mandible. This study suggests the importance of DDR1 in arthritis and periodontal function and may potentially inform disease mechanisms, wound healing, novel dental and periodontal therapies, and reconstruction of bone for dental and orthopedic purposes.
Academic Major: Biomedical Engineering