Small and porous ossicles, with flat stapes footplate and incudal fractures in the oim mouse model of osteogenesis imperfecta.

Abstract

Hearing loss affects approximately 70% of individuals with osteogenesis imperfecta (OI), a genetic connective tissue disorder characterized by bone fragility and deformities. No effective treatments exist for OI hearing loss, and its etiology is unknown limiting the development of new targeted therapies. This work investigates the impact of OI type I collagen mutations on the ossicle bone properties in the homozygous oim mouse model of severe OI, which is known to exhibit hearing loss. The morphology and porosity of the ossicles of 14-week-old oim and wild-type mice were analyzed using high-resolution synchrotron radiation microtomography. Additionally, the collagen fibers structure, bone tissue composition and mechanical properties were evaluated through second harmonic generation microscopy, Raman spectroscopy, and nanoindentation. The results demonstrated that oim ossicles are small, highly porous with an elevated lacunar number density, a flat stapes footplate and a small malleal processus brevis. One-in-two oim ossicles had incudomalleal joint abnormalities, exhibiting either a localized fracture in the incus head or a joint space widening. No differences were observed in collagen fibers structure, bone tissue composition and mechanical properties. These findings suggest that bone fractures observed in the oim incudes may contribute to their reported hearing loss. However, the underlying mechanism for these fractures' development remains to be investigated, as they do not appear to result from changes in bone tissue properties (collagen fibers organization, tissue composition or mechanical properties). Instead, they may be associated with joint space widening, and possibly altered ossicle chain kinematics.