Effects of Cathepsin K knock-out on the humerus of osteogenesis imperfecta mice

Details

Supervisors

Behets Wydemans, Catherine ; Roels, Thomas

Faculty

Faculté des sciences de la motricité

Degree label

Master [60] en kinésithérapie et réadaptation

Abstract

Osteogenesis imperfecta (OI) is a genetic disorder principally described by bone brittleness and fracture frequency and mainly due to a type I collagen dysfunction. Inhibition of Cathepsin K, a lysosomal protease responsible for the degradation of type 1 collagen, is already a treatment in post-menopausal osteoporosis. Our study aims to analyse the humerus of mice obtained after coupling Cathepsin K knock-out mice and Osteogenesis imperfecta mice. We analysed Wild type, OI, Cathepsin K KO and OI – Cathepsin K KO mice. Through four different experiments conducted, bone phenotype and biomechanical properties were analysed. Fracture rates were only observed in 33% of OI mice group. It was also noted that cortical width grows in OI - Cathepsin K KO mice compared to OI mice and that medullar width adapts in width. Biomechanical properties such as fracture force, bone hardness and modulus were evaluated. In said studies, trends were spotted that allowed speculation that OI – Cathepsin K KO mice does not decrease bone brittleness. Hardness and modulus results did not show significant difference. These results were not properly confirmed due to protocol errors although opened possibilities in developing new data allowing to understand in more depth this mutated mouse model. In conclusion, Cathepsin K could be a target in the treatment of osteogenesis imperfecta.