ArticleThe American journal of pathology2012
Chop (Ddit3) is essential for D469del-COMP retention and cell death in chondrocytes in an inducible transgenic mouse model of pseudoachondroplasia.
Article in The American journal of pathology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 43 citations in OpenAlex.
- Genotype-phenotype correlations in PSACH/EDM1 patients withFrontiers in endocrinology · 2026Review
- ElevatedInternational journal of molecular sciences · 2025Article
- DNA damage-inducible transcript 3 positively regulates RIPK1-mediated necroptosis.Cell death and differentiation · 2025Article
- Loss of CHOP Prevents Joint Degeneration and Pain in a Mouse Model of Pseudoachondroplasia.International journal of molecular sciences · 2024Article
- Curcumin and Resveratrol: Nutraceuticals with so Much Potential for Pseudoachondroplasia and Other ER-Stress Conditions.Biomolecules · 2024Review
- CurQ+, a Next-Generation Formulation of Curcumin, Ameliorates Growth Plate Chondrocyte Stress and Increases Limb Growth in a Mouse Model of Pseudoachondroplasia.International journal of molecular sciences · 2023Article
- Cartilage Oligomeric Matrix Protein, Diseases, and Therapeutic Opportunities.International journal of molecular sciences · 2022Review
- Clinical, Biochemical, Radiological, Genetic and Therapeutic Analysis of Patients with COMP Gene Variants.Calcified tissue international · 2022Article
- Primary Osteoarthritis Early Joint Degeneration Induced by Endoplasmic Reticulum Stress Is Mitigated by Resveratrol.The American journal of pathology · 2021Article
- Joint Degeneration in a Mouse Model of Pseudoachondroplasia: ER Stress, Inflammation, and Block of Autophagy.International journal of molecular sciences · 2021Article
- Article
- Mutant COMP shapes growth and development of skull and facial structures in mice and humans.Molecular genetics & genomic medicine · 2020Article
- Novel mTORC1 Mechanism Suggests Therapeutic Targets for COMPopathies.The American journal of pathology · 2019Article
- Article
- Mutant cartilage oligomeric matrix protein (COMP) compromises bone integrity, joint function and the balance between adipogenesis and osteogenesis.Matrix biology : journal of the International Society for Matrix Biology · 2018Article
- Skeletal Characterization of the Fgfr3 Mouse Model of Achondroplasia Using Micro-CT and MRI Volumetric Imaging.Scientific reports · 2018Article
- Review
- 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
- Antioxidant and anti-inflammatory agents mitigate pathology in a mouse model of pseudoachondroplasia.Human molecular genetics · 2015Article
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
Abstract
Cartilage oligomeric matrix protein (COMP), a secreted glycoprotein synthesized by chondrocytes, regulates proliferation and type II collagen assembly. Mutations in the COMP gene cause pseudoachondroplasia and multiple epiphyseal dysplasia. Previously, we have shown that expression of D469del-COMP in transgenic mice causes intracellular retention of D469del-COMP, thereby recapitulating pseudoachondroplasia chondrocyte pathology. This inducible transgenic D469del-COMP mouse is the only in vivo model to replicate the critical cellular and clinical features of pseudoachondroplasia. Here, we report developmental studies of D469del-COMP-induced chondrocyte pathology from the prenatal period to adolescence. D469del-COMP retention was limited prenatally and did not negatively affect the growth plate until 3 weeks after birth. Results of immunostaining, transcriptome analysis, and qRT-PCR suggest a molecular model in which D469del-COMP triggers apoptosis during the first postnatal week. By 3 weeks (when most chondrocytes are retaining D469del-COMP), inflammation, oxidative stress, and DNA damage contribute to chondrocyte cell death by necroptosis. Importantly, by crossing the D469del-COMP mouse onto a Chop null background (Ddit3 null), thereby eliminating Chop, the unfolded protein response was disrupted, thus alleviating both D469del-COMP intracellular retention and premature chondrocyte cell death. Chop therefore plays a significant role in processes that mediate D469del-COMP retention. Taken together, these results suggest that there may be an optimal window before the induction of significant D469del-COMP retention during which endoplasmic reticulum stress could be targeted.
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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.