Osteoblast Malfunction Caused by Cell Stress Response to Procollagen Misfolding in α2(I)-G610C Mouse Model of Osteogenesis Imperfecta.

ABSTRACT: Glycine (Gly) substitutions in collagen Gly-X-Y repeats disrupt folding of type I procollagen triple helix and cause severe bone fragility and malformations (osteogenesis imperfecta [OI]). However, these mutations do not elicit the expected endoplasmic reticulum (ER) stress response, in contrast to other protein-folding diseases. Thus, it has remained unclear whether cell stress and osteoblast malfunction contribute to the bone pathology caused by Gly substitutions. Here we used a mouse with a Gly610 to cysteine (Cys) substitution in the procollagen α2(I) chain to show that misfolded procollagen accumulation in the ER leads to an unusual form of cell stress, which is neither a conventional unfolded protein response (UPR) nor ER overload. Despite pronounced ER dilation, there is no upregula

SUBMITTER: Mirigian LS 

PROVIDER: S-EPMC5061462 | biostudies-literature | 2016 Aug

REPOSITORIES: biostudies-literature