Journal article

Effect of rapamycin on bone mass and strength in the alpha 2(I)-G610C mouse model of osteogenesis imperfecta

John F Bateman, Lisa Sampurno, Antonio Maurizi, Shireen R Lamande, Natalie A Sims, Tegan L Cheng, Aaron Schindeler, David G Little

JOURNAL OF CELLULAR AND MOLECULAR MEDICINE | WILEY | Published : 2019

Abstract

Osteogenesis imperfecta (OI) is commonly caused by heterozygous type I collagen structural mutations that disturb triple helix folding and integrity. This mutant-containing misfolded collagen accumulates in the endoplasmic reticulum (ER) and induces a form of ER stress associated with negative effects on osteoblast differentiation and maturation. Therapeutic induction of autophagy to degrade the mutant collagens could therefore be useful in ameliorating the ER stress and deleterious downstream consequences. To test this, we treated a mouse model of mild to moderate OI (α2(I) G610C) with dietary rapamycin from 3 to 8 weeks of age and effects on bone mass and mechanical properties were determi..

View full abstract