ArticleHuman molecular genetics2017
The chaperone activity of 4PBA ameliorates the skeletal phenotype of Chihuahua, a zebrafish model for dominant osteogenesis imperfecta.
Article in Human molecular genetics, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers.
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Who cites it
56 citing papers in PubMed, 84 citations in OpenAlex.
- Collagen secretion and maturation in osteogenesis imperfecta: Systematic review and meta-analysis.Bone reports · 2026Article
- Collagen hybridizing peptide to target in vivo misfolded collagen in OI zebrafish.Scientific reports · 2026Article
- OMICS Profiling Identifies Signatures of Senescence in Osteogenesis Imperfecta Osteoblasts Counteracted by 4-PBA.Journal of cellular and molecular medicine · 2026Article
- A New Perspective on Osteogenesis Imperfecta: From Cellular Mechanisms to the Systemic Impact of Collagen Dysfunction.International journal of molecular sciences · 2026Review
- Molecular drivers of osteogenesis imperfecta: a cellular and extracellular collagen disease.Clinical science (London, England : 1979) · 2025Review
- Combined antiresorptive and new anabolic drug approach in osteogenesis imperfecta zebrafish models.JBMR plus · 2025Article
- The chemical chaperone 4-phenylbutyric acid rescues molecular cell defects of COL3A1 mutations that cause vascular Ehlers Danlos Syndrome.Cell death discovery · 2025Article
- Comprehensive Review of Osteogenesis Imperfecta: Current Treatments and Future Innovations.Human gene therapy · 2025Review
- The administration of exogenous HSP47 as a collagen-specific therapeutic approach.JCI insight · 2025Article
- Bone cell differentiation and mineralization in wild-type and osteogenesis imperfecta zebrafish are compromised by per- and poly-fluoroalkyl substances (PFAS).Scientific reports · 2025Article
- Characterization of a Novel Col1a1Calcified tissue international · 2025Article
- Zebrafish Models for Skeletal and Extraskeletal Osteogenesis Imperfecta Features: Unveiling Pathophysiology and Paving the Way for Drug Discovery.Calcified tissue international · 2024Review
- Bone Quality and Mineralization and Effects of Treatment in Osteogenesis Imperfecta.Calcified tissue international · 2024Review
- Endoplasmic Reticulum Stress-Mediated Cell Death in Renal Fibrosis.Biomolecules · 2024Review
- New Perspectives of Therapies in Osteogenesis Imperfecta-A Literature Review.Journal of clinical medicine · 2024Review
- Emerging Landscape of Osteogenesis Imperfecta Pathogenesis and Therapeutic Approaches.ACS pharmacology & translational science · 2024Review
- Why Animal Experiments Are Still Indispensable in Bone Research: A Statement by the European Calcified Tissue Society.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2023Review
- Whole-Body Metabolism and the Musculoskeletal Impacts of Targeting Activin A and Myostatin in Severe Osteogenesis Imperfecta.JBMR plus · 2023Article
- Zebrafish Tric-b is required for skeletal development and bone cells differentiation.Frontiers in endocrinology · 2023Article
- Murine Animal Models in Osteogenesis Imperfecta: The Quest for Improving the Quality of Life.International journal of molecular sciences · 2022Review
Corrections and comments
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Authors and funding
16 authors at 7 institutions in 4 countries.
Funding
Abstract
Classical osteogenesis imperfecta (OI) is a bone disease caused by type I collagen mutations and characterized by bone fragility, frequent fractures in absence of trauma and growth deficiency. No definitive cure is available for OI and to develop novel drug therapies, taking advantage of a repositioning strategy, the small teleost zebrafish (Danio rerio) is a particularly appealing model. Its small size, high proliferative rate, embryo transparency and small amount of drug required make zebrafish the model of choice for drug screening studies, when a valid disease model is available. We performed a deep characterization of the zebrafish mutant Chihuahua, that carries a G574D (p.G736D) substitution in the α1 chain of type I collagen. We successfully validated it as a model for classical OI. Growth of mutants was delayed compared with WT. X-ray, µCT, alizarin red/alcian blue and calcein staining revealed severe skeletal deformity, presence of fractures and delayed mineralization. Type I collagen extracted from different tissues showed abnormal electrophoretic migration and low melting temperature. The presence of endoplasmic reticulum (ER) enlargement due to mutant collagen retention in osteoblasts and fibroblasts of mutant fish was shown by electron and confocal microscopy. Two chemical chaperones, 4PBA and TUDCA, were used to ameliorate the cellular stress and indeed 4PBA ameliorated bone mineralization in larvae and skeletal deformities in adult, mainly acting on reducing ER cisternae size and favoring collagen secretion. In conclusion, our data demonstrated that ER stress is a novel target to ameliorate OI phenotype; chemical chaperones such as 4PBA may be, alone or in combination, a new class of molecules to be further investigated for OI treatment.
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