ArticleHuman mutation2012
A novel form of chondrocyte stress is triggered by a COMP mutation causing pseudoachondroplasia.
Article in Human mutation, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 52 citations in OpenAlex.
- ElevatedInternational journal of molecular sciences · 2025Article
- From Protein Misfolding to Extracellular Matrix Disorganisation: Understanding Disease Pathology in Rare Skeletal Dysplasias.International journal of molecular sciences · 2025Review
- Cleavage of Cartilage Oligomeric Matrix Protein (COMP) by ADAMTS4 generates a neoepitope associated with osteoarthritis and other forms of degenerative joint disease.Matrix biology : journal of the International Society for Matrix Biology · 2025Article
- Thrombospondins: Conserved mediators and modulators of metazoan extracellular matrix.International journal of experimental pathology · 2024Review
- Cartilage Oligomeric Matrix Protein, Diseases, and Therapeutic Opportunities.International journal of molecular sciences · 2022Review
- Structure, evolution and expression of zebrafish cartilage oligomeric matrix protein (COMP, TSP5). CRISPR-Cas mutants show a dominant phenotype in myosepta.Frontiers in endocrinology · 2022Article
- Role of autophagy in intervertebral disc and cartilage function: implications in health and disease.Matrix biology : journal of the International Society for Matrix Biology · 2021Review
- Genetic Disorders of the Extracellular Matrix.Anatomical record (Hoboken, N.J. : 2007) · 2020Review
- New developments in chondrocyte ER stress and related diseases.F1000Research · 2020Review
- New perspectives on the treatment of skeletal dysplasia.Therapeutic advances in endocrinology and metabolism · 2020Review
- Mesencephalic astrocyte-derived neurotropic factor is an important factor in chondrocyte ER homeostasis.Cell stress & chaperones · 2019Article
- Pathogenic gene screening in 91 Chinese patients with short stature of unknown etiology with a targeted next-generation sequencing panel.BMC medical genetics · 2018Article
- Cartilage oligomeric matrix protein: COMPopathies and beyond.Matrix biology : journal of the International Society for Matrix Biology · 2018Review
- 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
- Genes uniquely expressed in human growth plate chondrocytes uncover a distinct regulatory network.BMC genomics · 2017Article
- Endoplasmic Reticulum Stress and Unfolded Protein Response in Cartilage Pathophysiology; Contributing Factors to Apoptosis and Osteoarthritis.International journal of molecular sciences · 2017Review
- Antisense Reduction of Mutant COMP Reduces Growth Plate Chondrocyte Pathology.Molecular therapy : the journal of the American Society of Gene Therapy · 2017Article
- New therapeutic targets in rare genetic skeletal diseases.Expert opinion on orphan drugs · 2015Article
- The utility of mouse models to provide information regarding the pathomolecular mechanisms in human genetic skeletal diseases: The emerging role of endoplasmic reticulum stress (Review).International journal of molecular medicine · 2015Review
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Authors and funding
9 authors at 2 institutions in 2 countries.
Funding
Abstract
Pseudoachondroplasia (PSACH) results from mutations in cartilage oligomeric matrix protein (COMP) and the p.D469del mutation within the type III repeats of COMP accounts for approximately 30% of PSACH. To determine disease mechanisms of PSACH in vivo, we introduced the Comp D469del mutation into the mouse genome. Mutant animals were normal at birth but grew slower than their wild-type littermates and developed short-limb dwarfism. In the growth plates of mutant mice chondrocyte columns were reduced in number and poorly organized, while mutant COMP was retained within the endoplasmic reticulum (ER) of cells. Chondrocyte proliferation was reduced and apoptosis was both increased and spatially dysregulated. Previous studies on COMP mutations have shown mutant COMP is co-localized with chaperone proteins, and we have reported an unfolded protein response (UPR) in mouse models of PSACH-MED (multiple epiphyseal dysplasia) harboring mutations in Comp (T585M) and Matn3, Comp etc (V194D). However, we found no evidence of UPR in this mouse model of PSACH. In contrast, microarray analysis identified expression changes in groups of genes implicated in oxidative stress, cell cycle regulation, and apoptosis, which is consistent with the chondrocyte pathology. Overall, these data suggest that a novel form of chondrocyte stress triggered by the expression of mutant COMP is central to the pathogenesis of PSACH.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.