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Functions of Discoidin Domain Receptor 1 (DDR1) in Periodontal Diseases

Zachariadou, Christina
http://orcid.org/0000-0002-6162-8817
http://rave.ohiolink.edu/etdc/view?acc_num=osu1703436574571901

Abstract Details

2024, Doctor of Philosophy, Ohio State University, Oral Biology.
Periodontal diseases affect the supporting tissues of teeth and lead to tooth mobility, tooth loss, and loss of masticatory function and quality of life. Approximately 56% of adults present with periodontitis, which manifests due to dysregulation between oral bacteria and host immune response. Discoidin Domain Receptor 1 (DDR1) is a transmembrane non-integrin collagen receptor that binds fibrillar collagens and collagen IV. It is widely expressed in epithelial, immune and bone cells. Binding to collagen and receptor activation leads to extracellular matrix remodeling and changes in cell behavior. Previous studies in our lab have shown that genetically modified DDR1-null mice (Ddr1-/-) present with progressive periodontal attachment and alveolar bone (AB) loss by 6 months of age. Thus, we hypothesized that DDR1 is necessary for maintenance of periodontal tissues and wound healing. Our first series of experiments (Aim 1) concluded that Ddr1-/- mice present with decreased junctional epithelium (the gingival epithelium mediating attachment of gingiva to the tooth surface) permeability compared to Ddr1+/+ mice. Additionally, epithelial migration over dorsal cutaneous wounds progressed faster in Ddr1-/- versus Ddr1+/+ mice. For our second aim, we used the ligature-induced periodontitis (LIP) model to predictably induce periodontitis in Ddr1+/+ and Ddr1-/- mice. At 3 days post-ligature (dpl), Ddr1-/- presented with higher bone loss than Ddr1+/+; the difference in bone loss disappeared at 5 and 8 dpl. Analysis of immune cells via flow cytometry showed that neutrophil and macrophage numbers were higher in gingiva and cardiac blood of Ddr1-/- mice at 3dpl. Finally, in aim 3, we employed Raman spectroscopy and showed that femurs of Ddr1-/- mice presented with decreased mineral-matrix ratio and increased pyridinoline cross-linking versus Ddr1+/+ mice at 50 days postnatal (dpn). We then proceeded to examine effects of DDR1 on AB resorption by employing the traumatic occlusion (TO) model that challenges periodontal ligament and alveolar bone. Our results showed that in the TO model, Ddr1-/- mice presented with increased alveolar bone loss and osteoclast numbers around molars than Ddr1+/+ mice. Additionally, the TO model led to dental abnormalities of mandibular molars suggesting that absence of DDR1 is associated with previously unrecognized enamel alterations predisposing to enamel breakdown, fracture and pulp necrosis. In summary, this is the first study to explore and identify mechanisms behind DDR1-induced periodontal destruction. Our research provides the first piece of evidence to support involvement of the collagen receptor DDR1 in the stability of periodontal tissues through its effects on epithelial permeability, immune cells and alveolar bone resorption.
Brian Foster (Advisor)
Gunjan Agarwal (Committee Member)
Parvathi Ranganathan (Committee Member)
Dimitris Tatakis (Committee Member)
Dentistry
DDR1, periodontitis, collagen, epithelium, immunity, bone

Recommended Citations

Citations

  • Zachariadou, C. (2024). Functions of Discoidin Domain Receptor 1 (DDR1) in Periodontal Diseases [Doctoral dissertation, Ohio State University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=osu1703436574571901

    APA Style (7th edition)

  • Zachariadou, Christina. Functions of Discoidin Domain Receptor 1 (DDR1) in Periodontal Diseases. 2024. Ohio State University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=osu1703436574571901.

    MLA Style (8th edition)

  • Zachariadou, Christina. "Functions of Discoidin Domain Receptor 1 (DDR1) in Periodontal Diseases." Doctoral dissertation, Ohio State University, 2024. http://rave.ohiolink.edu/etdc/view?acc_num=osu1703436574571901

    Chicago Manual of Style (17th edition)

osu1703436574571901
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