Endoplasmic reticulum stress is induced in growth plate hypertrophic chondrocytes in G610C mouse model of osteogenesis imperfecta.
Bone growth
Endoplasmic reticulum stress
Hypertrophic chondrocytes
Osteogenesis imperfecta
Journal
Biochemical and biophysical research communications
ISSN: 1090-2104
Titre abrégé: Biochem Biophys Res Commun
Pays: United States
ID NLM: 0372516
Informations de publication
Date de publication:
29 01 2019
29 01 2019
Historique:
received:
06
12
2018
accepted:
14
12
2018
pubmed:
24
12
2018
medline:
9
10
2019
entrez:
24
12
2018
Statut:
ppublish
Résumé
Osteogenesis imperfecta (OI) is a hereditary bone disorder most commonly caused by autosomal dominant mutations in genes encoding type I collagen. In addition to bone fragility, patients suffer from impaired longitudinal bone growth. It has been demonstrated that in OI, an accumulation of mutated type I collagen in the endoplasmic reticulum (ER) induces ER stress in osteoblasts, causing osteoblast dysfunction leading to bone fragility. We hypothesize that ER stress is also induced in the growth plate where bone growth is initiated, and examined a mouse model of dominant OI that carries a G610C mutation in the procollagen α2 chain. The results demonstrated that G610C OI mice had significantly shorter long bones with growth plate abnormalities including elongated total height and hypertrophic zone. Moreover, we found that mature hypertrophic chondrocytes expressed type I collagen and ER dilation was more pronounced compared to wild type littermates. The results from in vitro chondrocyte cultures demonstrated that the maturation of G610C OI hypertrophic chondrocytes was significantly suppressed and ER stress related genes were upregulated. Given that the alteration of hypertrophic chondrocyte activity often causes dwarfism, our findings suggest that hypertrophic chondrocyte dysfunction induced by ER stress may be an underlying cause of growth deficiency in G610C OI mice.
Identifiants
pubmed: 30579604
pii: S0006-291X(18)32760-8
doi: 10.1016/j.bbrc.2018.12.111
pmc: PMC6370306
mid: NIHMS1517095
pii:
doi:
Substances chimiques
Col1a2 protein, mouse
0
Collagen Type I
0
Types de publication
Journal Article
Research Support, N.I.H., Intramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
235-240Subventions
Organisme : Intramural NIH HHS
ID : ZIA HD000256-20
Pays : United States
Informations de copyright
Copyright © 2018 Elsevier Inc. All rights reserved.
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