Hypertrophic Chondrocytes Have a Limited Capacity to Cope with Increases in Endoplasmic Reticulum Stress without Triggering the Unfolded Protein Response
| Autor: | M. Helen Rajpar, Louise H. W. Kung, Raymond P. Boot-Handford, Michael D. Briggs |
|---|---|
| Rok vydání: | 2012 |
| Předmět: |
animal structures
Histology BiP (Grp78) Transgene Mutant Gene Dosage Osteoclasts Biology Osteochondrodysplasias medicine.disease_cause Mice 03 medical and health sciences Chondrocytes chondrodysplasia 0302 clinical medicine Osteogenesis Mutant protein growth plate medicine Animals Secretion Transgenes cartilage hypertrophic chondrocyte reproductive and urinary physiology Cell Size 030304 developmental biology Hemizygote 0303 health sciences Mutation Endoplasmic reticulum Homozygote Heterozygote advantage Articles unfolded protein response Embryo Mammalian Endoplasmic Reticulum Stress Mice Mutant Strains Cell biology collagen X embryonic structures Immunology Unfolded protein response Anatomy 030217 neurology & neurosurgery Collagen Type X |
| Zdroj: | Journal of Histochemistry and Cytochemistry |
| ISSN: | 1551-5044 0022-1554 |
| DOI: | 10.1369/0022155412458436 |
| Popis: | Mutations causing metaphyseal chondrodysplasia type Schmid (MCDS) (e.g., Col10a1p.N617K) induce the pathology by a mechanism involving increased endoplasmic reticulum (ER) stress triggering an unfolded protein response (UPR) in hypertrophic chondrocytes (Rajpar et al. 2009). Here we correlate the expression of mutant protein with the onset of the UPR and disease pathology (hypertrophic zone [HZ] expansion) in MCDS and ColXTg cog mouse lines from E14.5 to E17.5. Embryos homozygous for the Col10a1p.N617K mutation displayed a delayed secretion of mutant collagen X accompanied by a UPR at E14.5, delayed ossification of the primary center at E15.5, and an expanded HZ at E17.5. Heterozygote embryos expressed mutant collagen X from E14.5 but exhibited no evidence of a UPR or an HZ expansion until after E17.5. Embryos positive for the ER stress-inducing ColXTg cog allele expressed Tgcog at E14.5, but the onset of the UPR was not apparent until E15.5 in homozygous and E17.5 in hemizygous embryos. Only homozygous embryos exhibited an HZ expansion at E17.5. The differential onset of the UPR and pathology, dependent on mutation type and gene dosage, indicates that hypertrophic chondrocytes have a latent capacity to deal with ER stress, which must be exceeded to trigger the UPR and HZ expansion. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|