ArticleJCI insight2022
4PBA reduces growth deficiency in osteogenesis imperfecta by enhancing transition of hypertrophic chondrocytes to osteoblasts.
Article in JCI insight, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 32 citations in OpenAlex.
- Inhibition of EED enhances osteogenic differentiation and bone formation: a potential therapeutic strategy for osteogenesis imperfecta.JBMR plus · 2026Article
- Collagen secretion and maturation in osteogenesis imperfecta: Systematic review and meta-analysis.Bone reports · 2026Article
- Functional validation using a zebrafish model reclassifies the rare COL1A2 p.Gly418Ala variant as a cause of Osteogenesis Imperfecta.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 cell-nonautonomous heme acquisition pathway enables erythroid hemoglobinization under stress.bioRxiv : the preprint server for biology · 2026Article
- Modeling the chondrocyte-derived osteoblasts formation process reveals its molecular signature and regulation network.Bone research · 2026Article
- ElevatedInternational journal of molecular sciences · 2025Article
- Combined antiresorptive and new anabolic drug approach in osteogenesis imperfecta zebrafish models.JBMR plus · 2025Article
- Osteogenesis imperfecta: pathogenesis, classification, and treatment.Clinical pediatric endocrinology : case reports and clinical investigations : official journal of the Japanese Society for Pediatric Endocrinology · 2025Review
- Apolipoprotein E is a marker of all chondrocytes in the growth plate resting zone.Bone research · 2025Article
- The administration of exogenous HSP47 as a collagen-specific therapeutic approach.JCI insight · 2025Article
- Characterization of a Novel Col1a1Calcified tissue international · 2025Article
- Skeletal and Non-skeletal Phenotypes in Children with Osteogenesis Imperfecta.Calcified tissue international · 2024Review
- Skeletal pathology in mouse models of Gould syndrome is partially alleviated by genetically reducing TGFβ signaling.Matrix biology : journal of the International Society for Matrix Biology · 2024Article
- Article
- Apolipoprotein E is a novel marker for chondrocytes in the growth plate resting zone.Research square · 2024Article
- Depletion of b-series ganglioside prevents limb length discrepancy after growth plate injury.BMC musculoskeletal disorders · 2024Article
- RNA-based bone histomorphometry: method and its application to explaining postpubertal bone gain in a G610C mouse model of osteogenesis imperfecta.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2024Article
- New Perspectives of Therapies in Osteogenesis Imperfecta-A Literature Review.Journal of clinical medicine · 2024Review
- Altered Sox9 and FGF signaling gene expression in Aga2 OI mice negatively affects linear growth.JCI insight · 2023Article
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 3 countries.
Funding
Abstract
Short stature is a major skeletal phenotype in osteogenesis imperfecta (OI), a genetic disorder mainly caused by mutations in genes encoding type I collagen. However, the underlying mechanism is poorly understood, and no effective treatment is available. In OI mice that carry a G610C mutation in COL1A2, we previously found that mature hypertrophic chondrocytes (HCs) are exposed to cell stress due to accumulation of misfolded mutant type I procollagen in the endoplasmic reticulum (ER). By fate mapping analysis of HCs in G610C OI mice, we found that HCs stagnate in the growth plate, inhibiting translocation of HC descendants to the trabecular area and their differentiation to osteoblasts. Treatment with 4-phenylbutyric acid (4PBA), a chemical chaperone, restored HC ER structure and rescued this inhibition, resulting in enhanced longitudinal bone growth in G610C OI mice. Interestingly, the effects of 4PBA on ER dilation were limited in osteoblasts, and the bone fragility was not ameliorated. These results highlight the importance of targeting HCs to treat growth deficiency in OI. Our findings demonstrate that HC dysfunction induced by ER disruption plays a critical role in the pathogenesis of OI growth deficiency, which lays the foundation for developing new therapies for OI.
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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.