Transcriptional Profiling of Chondrodysplasia Growth Plate Cartilage Reveals Adaptive ER-Stress Networks That Allow Survival but Disrupt Hypertrophy
Trevor L Cameron, Katrina M Bell, Liliana Tatarczuch, Eleanor J Mackie, M Helen Rajpar, Ben T McDermott, Raymond P Boot-Handford, John F Bateman
PLoS One | PUBLIC LIBRARY SCIENCE | Published : 2011
Metaphyseal chondrodysplasia, Schmid type (MCDS) is characterized by mild short stature and growth plate hypertrophic zone expansion, and caused by collagen X mutations. We recently demonstrated the central importance of ER stress in the pathology of MCDS by recapitulating the disease phenotype by expressing misfolding forms of collagen X (Schmid) or thyroglobulin (Cog) in the hypertrophic zone. Here we characterize the Schmid and Cog ER stress signaling networks by transcriptional profiling of microdissected mutant and wildtype hypertrophic zones. Both models displayed similar unfolded protein responses (UPRs), involving activation of canonical ER stress sensors and upregulation of their do..View full abstract
Awarded by National Health and Medical Research Council of Australia
Awarded by European Commission
This work was supported by Project Grants (#491207, #607398) and a Research Fellowship (#1002797) to JFB from the National Health and Medical Research Council of Australia (www.nhmrc.gov.au) and by a grant to RBH from the European Commission (FP6; LSHMCT-2007-037471- ec.europa.eu/research/fp6/index_en.cfm). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.