He Xu1,2, Sydney A Lenhart3, Emily Y Chu2, Michael B Chavez4, Helen F Wimer5,6, Milena Dimori7, Martha J Somerman2, Roy Morello7,8,9, Brian L Foster4, Nan E Hatch3. 1. Department of Pediatric Dentistry, Peking University and School and Hospital of Stomatology, Beijing, China. 2. National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), National Institutes of Health (NIH), Bethesda, Maryland, USA. 3. Department of Orthodontics and Pediatric Dentistry, School of Dentistry, University of Michigan, Ann Arbor, Michigan, USA. 4. Division of Biosciences, College of Dentistry, The Ohio State University, Columbus, Ohio, USA. 5. Department of Vertebrate Zoology, National Museum of Natural History, Smithsonian Institution, Washington, District of Columbia, USA. 6. National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, Maryland, USA. 7. Department of Physiology & Biophysics, University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA. 8. Department of Orthopaedic Surgery, Center for Orthopaedic Research, University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA. 9. Division of Genetics, University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA.
Abstract
BACKGROUND: Inactivating mutations in the gene for cartilage-associated protein (CRTAP) cause osteogenesis imperfecta type VII in humans, with a phenotype that can include craniofacial defects. Dental and craniofacial manifestations have not been a focus of case reports to date. We analyzed the craniofacial and dental phenotype of Crtap-/- mice by skull measurements, micro-computed tomography (micro-CT), histology, and immunohistochemistry. RESULTS: Crtap-/- mice exhibited a brachycephalic skull shape with fusion of the nasofrontal suture and facial bones, resulting in mid-face retrusion and a class III dental malocclusion. Loss of CRTAP also resulted in decreased dentin volume and decreased cellular cementum volume, though acellular cementum thickness was increased. Periodontal dysfunction was revealed by decreased alveolar bone volume and mineral density, increased periodontal ligament (PDL) space, ectopic calcification within the PDL, bone-tooth ankylosis, altered immunostaining of extracellular matrix proteins in bone and PDL, increased pSMAD5, and more numerous osteoclasts on alveolar bone surfaces. CONCLUSIONS: Crtap-/- mice serve as a useful model of the dental and craniofacial abnormalities seen in individuals with osteogenesis imperfecta type VII.
BACKGROUND: Inactivating mutations in the gene for cartilage-associated protein (CRTAP) cause osteogenesis imperfecta type VII in humans, with a phenotype that can include craniofacial defects. Dental and craniofacial manifestations have not been a focus of case reports to date. We analyzed the craniofacial and dental phenotype of Crtap-/- mice by skull measurements, micro-computed tomography (micro-CT), histology, and immunohistochemistry. RESULTS:Crtap-/- mice exhibited a brachycephalic skull shape with fusion of the nasofrontal suture and facial bones, resulting in mid-face retrusion and a class III dental malocclusion. Loss of CRTAP also resulted in decreased dentin volume and decreased cellular cementum volume, though acellular cementum thickness was increased. Periodontal dysfunction was revealed by decreased alveolar bone volume and mineral density, increased periodontal ligament (PDL) space, ectopic calcification within the PDL, bone-tooth ankylosis, altered immunostaining of extracellular matrix proteins in bone and PDL, increased pSMAD5, and more numerous osteoclasts on alveolar bone surfaces. CONCLUSIONS:Crtap-/- mice serve as a useful model of the dental and craniofacial abnormalities seen in individuals with osteogenesis imperfecta type VII.
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