ArticleDisease models & mechanisms2013
A novel transgenic mouse model of growth plate dysplasia reveals that decreased chondrocyte proliferation due to chronic ER stress is a key factor in reduced bone growth.
Article in Disease models & mechanisms, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 25 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
- Proteomic analysis of hydrogen peroxide-treated human chondrocytes shows endoplasmic reticulum stress, cytoskeleton remodeling, and altered secretome composition.Cell communication and signaling : CCS · 2025Article
- Integration of Network Pharmacology, Molecular Docking, and Experimental Validation to Identify the Effect of EGCG on Alleviating Chondrocyte Inflammatory Damage by Targeting ER Stress-STAT3 Crosstalk.Journal of inflammation research · 2025Article
- Article
- 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
- Calcium activated nucleotidase 1 (CANT1) is critical for glycosaminoglycan biosynthesis in cartilage and endochondral ossification.Matrix biology : journal of the International Society for Matrix Biology · 2019Article
- Mesencephalic astrocyte-derived neurotropic factor is an important factor in chondrocyte ER homeostasis.Cell stress & chaperones · 2019Article
- Hemiepiphysiodesis stapling induces ER stress apoptosis and autophagy in rat growth plates.American journal of translational research · 2019Article
- Cartilage oligomeric matrix protein: COMPopathies and beyond.Matrix biology : journal of the International Society for Matrix Biology · 2018Review
- The Chemical Chaperone, PBA, Reduces ER Stress and Autophagy and Increases Collagen IV α5 Expression in Cultured Fibroblasts From Men With X-Linked Alport Syndrome and Missense Mutations.Kidney international reports · 2017Article
- Sex-Linked Skeletal Phenotype of Lysyl Oxidase Like-1 Mutant Mice.Calcified tissue international · 2016Article
- 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
- Article
- Emerging regulators of the inflammatory process in osteoarthritis.Nature reviews. Rheumatology · 2015Review
- Extracellular matrix and developing growth plate.Current osteoporosis reports · 2014Review
- A novel mutation in DDR2 causing spondylo-meta-epiphyseal dysplasia with short limbs and abnormal calcifications (SMED-SL) results in defective intra-cellular trafficking.BMC medical genetics · 2014Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
Abstract
Disease mechanisms leading to different forms of chondrodysplasia include extracellular matrix (ECM) alterations and intracellular stress resulting in abnormal changes to chondrocyte proliferation and survival. Delineating the relative contribution of these two disease mechanisms is a major challenge in understanding disease pathophysiology in genetic skeletal diseases and a prerequisite for developing effective therapies. To determine the influence of intracellular stress and changes in chondrocyte phenotype to the development of chondrodysplasia, we targeted the expression of the G2320R mutant form of thyroglobulin to the endoplasmic reticulum (ER) of resting and proliferating chondrocytes. Previous studies on this mutant protein have shown that it induces intracellular aggregates and causes cell stress and death in the thyroid gland. The expression and retention of this exogenous mutant protein in resting and proliferating chondrocytes resulted in a chronic cell stress response, growth plate dysplasia and reduced bone growth, without inducing any alterations to the architecture and organization of the cartilage ECM. More significantly, the decreased bone growth seemed to be the direct result of reduced chondrocyte proliferation in the proliferative zone of growth plates in transgenic mice, without transcriptional activation of a classical unfolded protein response (UPR) or apoptosis. Overall, these data show that mutant protein retention in the ER of resting and proliferative zone chondrocytes is sufficient to cause disrupted bone growth. The specific disease pathways triggered by mutant protein retention do not necessarily involve a prototypic UPR, but all pathways impact upon chondrocyte proliferation in the cartilage growth plate.
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