Craniofacial dysmorphism of osteogenesis imperfecta mouse and effect of cathepsin K knockout: Preliminary craniometry observations.

ABSTRACT

OBJECTIVES: In addition to bone fragility, patients with osteogenesis imperfecta (OI) type III have typical craniofacial abnormalities, such as a triangular face and maxillary micrognathism. However, in the osteogenesis imperfecta mouse (oim), a validated model of OI type III, few descriptions exist of craniofacial phenotype. Treatment of OI mostly consists of bisphosphonate administration. Cathepsin K inhibition has been tested as a promising therapeutic approach for osteoporosis and positive results were observed in long bones of cathepsin K knocked out oim (oim/CatK-/-). This craniometry study aimed to highlight the craniofacial characteristics of oim and Cathepsin K KO mouse. MATERIALS AND METHODS: We analyzed the craniofacial skeleton of 51 mice distributed in 4 genotype groups Wt (control), oim, CatK-/-, oim/CatK-/-. The mice were euthanized at 13 weeks and their heads were analyzed using densitometric (pQCT), X-ray cephalometric, and histomorphometric methods. RESULTS: The craniofacial skeleton of the oim mouse is frailer than the Wt one, with a reduced thickness and mineral density of the cranial vault and mandibular ramus. Different cephalometric data attest a dysmorphism similar to the one observed in humans with OI type III. Those abnormalities were not improved in the oim/CatK-/- group. CONCLUSION: These results suggest that oim mouse could serve as a complete model of the human OI type III, including the craniofacial skeleton. They also suggest that invalidation of cathepsin K has no impact on the craniofacial abnormalities of the oim model.