ArticleHuman molecular genetics2018
Carbamazepine reduces disease severity in a mouse model of metaphyseal chondrodysplasia type Schmid caused by a premature stop codon (Y632X) in the Col10a1 gene.
Article in Human molecular genetics, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 26 citations in OpenAlex.
- Integrated stress signaling pathways promote adaptive reprogramming for chondrocyte survival in Metaphyseal Chondrodysplasia Type Schmid.Bone research · 2026Article
- A truncated COL10A1 protein causes Schmid metaphyseal chondrodysplasia via protein downregulation and impairing α1 trimer formation and secretion.Functional & integrative genomics · 2026Article
- COL10A1 beyond skeletal development: a hypertrophic chondrocyte-specific collagen emerging as a potential biomarker and tumor microenvironment regulator in solid cancers.American journal of cancer research · 2026Review
- Clinical, Molecular Characteristics, and Genotype-Phenotype Relationships of Metaphyseal Chondrodysplasia Type Schmid.Calcified tissue international · 2025Article
- From Protein Misfolding to Extracellular Matrix Disorganisation: Understanding Disease Pathology in Rare Skeletal Dysplasias.International journal of molecular sciences · 2025Review
- EndoCompass Project: Research Roadmap for Calcium and Bone Endocrinology.Hormone research in paediatrics · 2025Review
- Normal Bone Matrix Mineralization but Altered Growth Plate Morphology in the LmnaAging and disease · 2024Article
- A Collagen10a1 mutation disrupts cell polarity in a medaka model for metaphyseal chondrodysplasia type Schmid.iScience · 2024Article
- NaNature · 2024Article
- Hypertrophic chondrocytes at the junction of musculoskeletal structures.Bone reports · 2023Article
- Interventions for improving clinical outcomes and health-related quality-of-life for people living with skeletal dysplasias: an evidence gap map.Quality of life research : an international journal of quality of life aspects of treatment, care and rehabilitation · 2023Review
- Curcumin Reduces Pathological Endoplasmic Reticulum Stress through Increasing Proteolysis of Mutant Matrilin-3.International journal of molecular sciences · 2023Article
- The effect of carbamazepine on bone structure and strength in control and osteogenesis imperfecta (Col1a2Journal of cellular and molecular medicine · 2022Article
- Collagen misfolding mutations: the contribution of the unfolded protein response to the molecular pathology.Connective tissue research · 2022Review
- 4PBA reduces growth deficiency in osteogenesis imperfecta by enhancing transition of hypertrophic chondrocytes to osteoblasts.JCI insight · 2022Article
- "Lessons from Rare Forms of Osteoarthritis".Calcified tissue international · 2021Review
- Differentiation of Hypertrophic Chondrocytes from Human iPSCs for the In Vitro Modeling of Chondrodysplasias.Stem cell reports · 2021Article
- New developments in chondrocyte ER stress and related diseases.F1000Research · 2020Review
- Identification of two novel COL10A1 heterozygous mutations in two Chinese pedigrees with Schmid-type metaphyseal chondrodysplasia.BMC medical genetics · 2019Article
- Cartilage endoplasmic reticulum stress may influence the onset but not the progression of experimental osteoarthritis.Arthritis research & therapy · 2019Article
Corrections and comments
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Authors and funding
3 authors at 3 institutions in 2 countries.
Funding
Abstract
Mutations, mostly in the region of the COL10A1 gene encoding the C-terminal non-collagenous domain, cause the dwarfism metaphyseal chondrodysplasia type Schmid (MCDS). In most cases, the disease mechanism involves the misfolding of the mutant protein causing increased endoplasmic reticulum (ER) stress and an unfolded protein response (UPR). However, in an iliac crest biopsy, the COL10A1 p.Y632X mutation was found to produce instability of the mutant mRNA such that little mutant protein may be produced. To investigate the disease mechanism further, a gene-targeted mouse model of the Col10a1 p.Y632X mutation was generated. In this model, the mutant mRNA showed no instability, and in mice heterozygous for the mutation, mutant and wild-type mRNAs were present at equal concentrations. The protein was translated from the mutant allele and retained within the cell, triggering increased ER stress and a UPR. The mutation produced a relatively severe form of MCDS. Nevertheless, treatment of the mice with carbamazepine (CBZ), a drug which stimulates intracellular proteolysis and alleviates ER stress, effectively reduced the disease severity in this model of MCDS caused by a premature stop codon in the Col10a1 gene. Specifically, the drug reduced ER stress in the growth plate, restored growth plate architecture toward the wild-type state, significantly increased bone growth and within 2 weeks of treatment corrected the MCDS-induced hip distortion. These results indicate that CBZ is likely to be effective in ongoing clinical trials against all forms of MCDS whether caused by premature stop codons or substitutions.
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