Journal article

XBP1-Independent UPR Pathways Suppress C/EBP-beta Mediated Chondrocyte Differentiation in ER-Stress Related Skeletal Disease

Trevor L Cameron, Katrina M Bell, Irma L Gresshoff, Lisa Sampurno, Lorna Mullan, Joerg Ermann, Laurie H Glimcher, Raymond P Boot-Handford, John F Bateman

PLOS GENETICS | PUBLIC LIBRARY SCIENCE | Published : 2015

Abstract

Schmid metaphyseal chondrodysplasia (MCDS) involves dwarfism and growth plate cartilage hypertrophic zone expansion resulting from dominant mutations in the hypertrophic zone collagen, Col10a1. Mouse models phenocopying MCDS through the expression of an exogenous misfolding protein in the endoplasmic reticulum (ER) in hypertrophic chondrocytes have demonstrated the central importance of ER stress in the pathology of MCDS. The resultant unfolded protein response (UPR) in affected chondrocytes involved activation of canonical ER stress sensors, IRE1, ATF6, and PERK with the downstream effect of disrupted chondrocyte differentiation. Here, we investigated the role of the highly conserved IRE1/X..

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Grants

Awarded by National Health and Medical Research Council of Australia grant


Awarded by NIH


Awarded by EUNICE KENNEDY SHRIVER NATIONAL INSTITUTE OF CHILD HEALTH & HUMAN DEVELOPMENT


Funding Acknowledgements

This work was funded by the National Health and Medical Research Council of Australia grant #607398 (JFB), the Victorian Government's Operational Infrastructure Support Program, and NIH Grant HD055601 (LHG). The funders had no role in study design, collection, analysis or interpretation of data, or writing the manuscript, or decision to submit the manuscript.