ArticleThe Journal of biological chemistry
4-Phenylbutyric acid enhances the mineralization of osteogenesis imperfecta iPSC-derived osteoblasts.
Article in The Journal of biological chemistry. 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, 30 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
- Post-translational modifications of collagen type I in osteogenesis imperfecta: Systematic review and meta-analysis.Bone reports · 2026Article
- Diverging pathomechanisms underlying collagen I-related and MBTPS2-related osteogenesis imperfecta: insights from patient-derived fibroblasts and iPSC-based modelling of bone.Frontiers in endocrinology · 2026Article
- Osteogenesis imperfecta: pathogenesis, classification, and treatment.Clinical pediatric endocrinology : case reports and clinical investigations : official journal of the Japanese Society for Pediatric Endocrinology · 2025Review
- The structural basis for the human procollagen lysine hydroxylation and dual-glycosylation.Nature communications · 2025Article
- Collagen formation, function and role in kidney disease.Nature reviews. Nephrology · 2025Review
- Characterization of a Novel Col1a1Calcified tissue international · 2025Article
- Modeling of skeletal development and diseases using human pluripotent stem cells.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2024Review
- In Vitro Modelling of Osteogenesis Imperfecta with Patient-Derived Induced Mesenchymal Stem Cells.International journal of molecular sciences · 2024Article
- ERS Mediated by GRP-78/PERK/CHOP Signaling Is Involved in Fluoride-Induced Ameloblast Apoptosis.Biological trace element research · 2024Article
- New Perspectives of Therapies in Osteogenesis Imperfecta-A Literature Review.Journal of clinical medicine · 2024Review
- The Chemistry and Biology of Collagen Hybridization.Journal of the American Chemical Society · 2023Review
- Rosemary Extract-Induced Autophagy and Decrease in Accumulation of Collagen Type I in Osteogenesis Imperfecta Skin Fibroblasts.International journal of molecular sciences · 2022Article
- Up-regulated IL-17 and Tnf signaling in bone marrow cells of young male osteogenesis imperfecta mice.PeerJ · 2022Article
- Collagen transport and related pathways in Osteogenesis Imperfecta.Human genetics · 2021Review
- Targeting cellular stress in vitro improves osteoblast homeostasis, matrix collagen content and mineralization in two murine models of osteogenesis imperfecta.Matrix biology : journal of the International Society for Matrix Biology · 2021Article
- Inhibition of Endoplasmic Reticulum Stress by 4-Phenyl Butyric Acid Presents Therapeutic Effects on Periodontitis: Experimental StudiesStem cells international · 2021Article
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Osteogenesis imperfecta (OI) is a heritable brittle bone disease mainly caused by mutations in the two type I collagen genes. Collagen synthesis is a complex process including trimer formation, glycosylation, secretion, extracellular matrix (ECM) formation, and mineralization. Using OI patient-derived fibroblasts and induced pluripotent stem cells (iPSCs), we investigated the effect of 4-phenylbutyric acid (4-PBA) on collagen synthesis to test its potential as a new treatment for OI. Endoplasmic reticulum (ER) retention of type I collagen was observed by immunofluorescence staining in OI patient-derived fibroblasts with glycine substitution and exon skipping mutations. Liquid chromatography-mass spectrometry analysis revealed excessive glycosylation of secreted type I collagen at the specific sites in OI cells. The misfolding of the type I collagen triple helix in the ECM was demonstrated by the incorporation of heat-dissociated collagen hybridizing peptide in OI cells. Type I collagen was produced excessively by OI fibroblasts with a glycine mutation, but this excessive production was normalized when OI fibroblasts were cultured on control fibroblast-derived ECM. We also found that mineralization was impaired in osteoblasts differentiated from OI iPSCs. In summary, treatment with 4-PBA normalizes the excessive production of type I collagen, reduces ER retention, partially improves misfolding of the type I collagen helix in ECM, and improves osteoblast mineralization. Thus, 4-PBA may improve not only ER retention, but also type I collagen synthesis and mineralization in human cells from OI patients.
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