Behets Wydemans, CatherineChretien, AntoineAndré, GrégoireDemoulin, AntoineAntoineDemoulin2025-05-142025-05-142025-05-142024https://hdl.handle.net/2078.2/36674Osteogenesis imperfecta (OI) is a rare genetic disease affecting connective tissues, whose main clinical manifestations are skeletal dysplasia and bone fragility. Current medications rely on the use of anti-resorptive drugs, such as bisphosphonate, however, their long-term use induces side-effects. The development of a new treatment improving bone quality should be relevant to act in synergy with current treatments. This study investigated the oral administration effects of a flavonoid (c-molecule) on bone properties of osteogenesis imperfecta mice (oim), as compared to wild type control (WTC, n=11) and treated ones (WTT, n=10). In parallel, the dose effect was assessed with three different groups of oim mice, treated with the c-molecule at 0.5 mg/mL (OIT0.5, n=11), 2.5 mg/mL (OIT2.5, n=12) or 10.0 mg/mL (OIT10.0, n=10), from 5 to 17 weeks of life. The fibre organisation in oim tendon was also assessed in untreated mice. Throughout the experiment, oim mice were lighter than WT ones. Treated oim mice presented fewer fractures than oim control ones (OIC, n=12) at 11 and 17 weeks of life. PQCT analyses showed reduced cross-sectional area (CSA), cortical area and stress-strain index (SSI) in oim mice femur as compared to WT ones. Despite the bone mineral density (BMD) and cortical BMD were lower in oim mice than in WT mice, the OIT10.0 group had no significant difference in mineral content with WT mice. Stiffness, yield load, maximum load and ultimate load were significantly lower in oim than WT femurs. The crystallinity was significantly reduced in the mid cortical of femurs in oim groups as compared to WT mice. In the outer cortical area, the carbonate substitution of hydroxyapatite crystals was higher in WTC, WTT and OIT10.0 groups, and their content in organic molecules was lower. In almost all lumbar vertebrae, the BMD was lower in oim mice than in WT mice apart from the OIT10.0 group. The total area of vertebrae was only lower in the L1 of oim mice except for the OIT10.0 group. For L1 and L2, the cortical area was lower in oim mice except for the OIT10.0 group. Concerning the oim tendon, the fibre organisation did not highlight difference with WTC mice. In the future, it will be interesting to better understand how the c-molecule decreased the fracture rate of treated oim mice and to continue the analyses on mice vertebrae.bonetendonoimpolyphenolosteogenesis imperfectatext::thesis::master thesisthesis:44265