title: Ultra-structural defects cause low bone matrix stiffness despite high mineralization in osteogenesis imperfecta mice.
abstract: Bone is a complex material with a hierarchical multi-scale organization from the molecule to the organ scale. The genetic bone disease, osteogenesis imperfecta, is primarily caused by mutations in the collagen type I genes, resulting in bone fragility. Because the basis of the disease is molecular with ramifications at the whole bone level, it provides a platform for investigating the relationship between structure, composition, and mechanics throughout the hierarchy. Prior studies have individually shown that OI leads to: 1. increased bone mineralization, 2. decreased elastic modulus, and 3. smaller apatite crystal size. However, these have not been studied together and the mechanism for how mineral structure influences tissue mechanics has not been identified. This lack of understanding inhibits the development of more accurate models and therapies. To address this research gap, we used a mouse model of the disease (oim) to measure these outcomes together in order to propose an underlying mechanism for the changes in properties. Our main finding was that despite increased mineralization, oim bones have lower stiffness that may result from the poorly organized mineral matrix with significantly smaller, highly packed and disoriented apatite crystals. Using a composite framework, we interpret the lower oim bone matrix elasticity observed as the result of a change in the aspect ratio of apatite crystals and a disruption of the crystal connectivity.
authors.affiliation: Department of Bioengineering, Imperial College London, London,SW7-2AZ, UK. m.vanleene@imperial.ac.uk
authors.forename: Maximilien
authors.initials: M
authors.lastname: Vanleene
authors.forename: Alexandra
authors.initials: A
authors.lastname: Porter
authors.forename: Pascale-Valerie
authors.initials: PV
authors.lastname: Guillot
authors.forename: Alan
authors.initials: A
authors.lastname: Boyde
authors.forename: Michelle
authors.initials: M
authors.lastname: Oyen
authors.forename: Sandra
authors.initials: S
authors.lastname: Shefelbine
mesh_terms: D000818:Animals; D001031:Apatites / Q000737:chemistry; D001696:Biomechanical Phenomena; D015519:Bone Density; D001857:Bone Matrix / Q000503:physiopathology* / Q000648:ultrastructure*; D003460:Crystallization; D004195:Disease Models, Animal; D055119:Elastic Modulus; D005260:Female; D008297:Male; D051379:Mice; D008817:Mice, Mutant Strains; D008855:Microscopy, Electron, Scanning; D046529:Microscopy, Electron, Transmission; D010013:Osteogenesis Imperfecta / Q000235:genetics / Q000473:pathology* / Q000503:physiopathology*; D013314:Stress, Mechanical
chemical_list: D001031:Apatites