ArticlePloS one2015
Increased classical endoplasmic reticulum stress is sufficient to reduce chondrocyte proliferation rate in the growth plate and decrease bone growth.
Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 38 citations in OpenAlex.
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- Thrombospondins: Conserved mediators and modulators of metazoan extracellular matrix.International journal of experimental pathology · 2024Review
- Novel Function of Osteocalcin in Chondrocyte Differentiation and Endochondral Ossification Revealed on a CRISPR/Cas9International journal of molecular sciences · 2024Article
- Curcumin and Resveratrol: Nutraceuticals with so Much Potential for Pseudoachondroplasia and Other ER-Stress Conditions.Biomolecules · 2024Review
- Early Resveratrol Treatment Mitigates Joint Degeneration and Dampens Pain in a Mouse Model of Pseudoachondroplasia (PSACH).Biomolecules · 2023Article
- The natural product salicin alleviates osteoarthritis progression by binding to IRE1α and inhibiting endoplasmic reticulum stress through the IRE1α-IκBα-p65 signaling pathway.Experimental & molecular medicine · 2022Article
- PDIA3/ERp57 promotes a matrix-rich secretome that stimulates fibroblast adhesion through CCN2.American journal of physiology. Cell physiology · 2022Article
- "Lessons from Rare Forms of Osteoarthritis".Calcified tissue international · 2021Review
- Impaired chondrocyte U3 snoRNA expression in osteoarthritis impacts the chondrocyte protein translation apparatus.Scientific reports · 2020Article
- New developments in chondrocyte ER stress and related diseases.F1000Research · 2020Review
- Cartilage endoplasmic reticulum stress may influence the onset but not the progression of experimental osteoarthritis.Arthritis research & therapy · 2019Article
- A novel mutation in exon 11 of COMP gene in a Chinese family with pseudoachondroplasia.Genes & diseases · 2019Article
- Review
- Carbamazepine reduces disease severity in a mouse model of metaphyseal chondrodysplasia type Schmid caused by a premature stop codon (Y632X) in the Col10a1 gene.Human molecular genetics · 2018Article
- Paradoxical roles of ATF6α and ATF6β in modulating disease severity caused by mutations in collagen X.Matrix biology : journal of the International Society for Matrix Biology · 2018Article
- Different Forms of ER Stress in Chondrocytes Result in Short Stature Disorders and Degenerative Cartilage Diseases: New Insights by Cartilage-Specific ERp57 Knockout Mice.Oxidative medicine and cellular longevity · 2018Review
- Soluble Epoxide Hydrolase Pharmacological Inhibition Decreases Alveolar Bone Loss by Modulating Host Inflammatory Response, RANK-Related Signaling, Endoplasmic Reticulum Stress, and Apoptosis.The Journal of pharmacology and experimental therapeutics · 2017Article
- Endoplasmic Reticulum Stress and Unfolded Protein Response in Cartilage Pathophysiology; Contributing Factors to Apoptosis and Osteoarthritis.International journal of molecular sciences · 2017Review
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Mutations in genes encoding cartilage oligomeric matrix protein and matrilin-3 cause a spectrum of chondrodysplasias called multiple epiphyseal dysplasia (MED) and pseudoachondroplasia (PSACH). The majority of these diseases feature classical endoplasmic reticulum (ER) stress and activation of the unfolded protein response (UPR) as a result of misfolding of the mutant protein. However, the importance and the pathological contribution of ER stress in the disease pathogenesis are unknown. The aim of this study was to investigate the generic role of ER stress and the UPR in the pathogenesis of these diseases. A transgenic mouse line (ColIITgcog) was generated using the collagen II promoter to drive expression of an ER stress-inducing protein (Tgcog) in chondrocytes. The skeletal and histological phenotypes of these ColIITgcog mice were characterised. The expression and intracellular retention of Tgcog induced ER stress and activated the UPR as characterised by increased BiP expression, phosphorylation of eIF2α and spliced Xbp1. ColIITgcog mice exhibited decreased long bone growth and decreased chondrocyte proliferation rate. However, there was no disruption of chondrocyte morphology or growth plate architecture and perturbations in apoptosis were not apparent. Our data demonstrate that the targeted induction of ER stress in chondrocytes was sufficient to reduce the rate of bone growth, a key clinical feature associated with MED and PSACH, in the absence of any growth plate dysplasia. This study establishes that classical ER stress is a pathogenic factor that contributes to the disease mechanism of MED and PSACH. However, not all the pathological features of MED and PSACH were recapitulated, suggesting that a combination of intra- and extra-cellular factors are likely to be responsible for the disease pathology as a whole.
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