Pole of Morphology, Institute of Experimental and Clinical Research (IREC), UCLouvain, 1200 Brussels, Belgium.
Univ Angers, Nantes Université, Oniris, Inserm, RMeS, REGOS, SFR ICAT, F-49000 Angers, France.
Int J Mol Sci. 2022 Sep 1;23(17):9928. doi: 10.3390/ijms23179928.
Osteogenesis imperfecta (OI) is a genetic disorder of connective tissue characterized by low bone mass and spontaneous fractures, as well as extra-skeletal manifestations, such as dental abnormalities, blue sclera, hearing loss and joint hypermobility. Tendon ruptures have been reported in OI patients. Here, we characterized the biomechanical, structural and tissue material properties of bone and tendon in 5-week-old female osteogenesis imperfecta mice (oim), a validated model of severe type III OI, and compared these data with age- and sex-matched WT littermates. Oim tendons were less rigid and less resistant than those of WT mice. They also presented a significantly higher rate of pentosidine, without significant modification of enzymatic crosslinking. The oim bones were less resistant and avulsion fractures were evident at high tendinous stress areas. Alterations of trabecular and cortical bone microarchitectures were noticed in young female oim. Bone tissue material properties were also modified, with a less mature and more mineralized matrix in association with lower collagen maturity. Our data suggest that the tendon-to-bone unit is affected in young oim mice, which could explain tendon ruptures and bone fragility observed in OI patients.
成骨不全症(OI)是一种结缔组织遗传疾病,其特征是骨量低、自发性骨折以及骨骼外表现,如牙齿异常、巩膜蓝色、听力损失和关节过度活动。OI 患者已有肌腱断裂的报道。在这里,我们对 5 周龄雌性成骨不全症小鼠(oim)的骨骼和肌腱的生物力学、结构和组织材料特性进行了表征,oim 是一种经过验证的严重 III 型 OI 模型,并将这些数据与年龄和性别匹配的 WT 同窝仔鼠进行了比较。oim 肌腱比 WT 小鼠的肌腱刚性更小、抗断裂能力更低。它们还表现出更高的戊糖含量,而酶交联的修饰没有显著改变。在高肌腱应力区域可见 oim 骨骼的抗断裂能力降低和撕脱性骨折。年轻雌性 oim 的骨小梁和皮质骨微结构也发生了改变。骨组织材料特性也发生了改变,与胶原成熟度降低相关的是基质更不成熟且矿化程度更高。我们的数据表明,年轻的 oim 小鼠的肌腱-骨单位受到影响,这可以解释 OI 患者中观察到的肌腱断裂和骨骼脆弱。