NIH Research Festival
Background Osteogenesis imperfecta (OI) is a heritable bone dysplasia caused by defects in collagen processing and synthesis. Autosomal dominant (AD) forms of OI involve mutations in COL1A1 or COL1A2, genes encoding collagen proteins incorporated into the collagen heterotrimer. Autosomal recessive (AR) forms of OI result from mutations affecting proteins involved in collagen post-translational modification, cross-linking, stabilization, and/or chaperoning of the collagen fibril. Effects of OI on tooth root and periodontal development are not well documented in humans or mouse models. We hypothesized that OI would alter periodontal tissues because the periodontal complex of cementum-PDL-bone is collagen-based, under continuous mechanical stress from forces of occlusion, and remodels throughout life. Methods: Mouse models for AD (Brtl+/- and Gly610Cys+/- mice) and AR (Crtap-/- and Ppib-/- mice) OI were studied at multiple ages. Mandibles were analyzed by radiological (X-ray and microcomputed tomography) and histologic (H&E staining, immunohistochemistry and picrosirius red staining) methods. Results: Compared to controls, AD Brtl+/- mice featured thinner dentin, ectopic pulp calcification and alveolar bone defects, while Gly610Cys+/- mice had relatively normal morphology at young ages. AR models exhibited significant periodontal changes. Both Crtap-/- and Ppib-/- mice featured parallel phenotypes including increased acellular cementum, and reduced cellular cementum, dentin width and root length. Conclusion: For the first time, we identify periodontal changes in mice resulting from AR and AD OI. Changes reflect developmental defects, as well as altered function and remodeling or later in life. These findings will provide insights into oral-dental health of human subjects with OI.
Scientific Focus Area: Institute, Center, and Scientific Directors
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