ArticleJournal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research2016
Osteoblast Malfunction Caused by Cell Stress Response to Procollagen Misfolding in α2(I)-G610C Mouse Model of Osteogenesis Imperfecta.
Article in Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 62 papers.
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Who cites it
62 citing papers in PubMed, 87 citations in OpenAlex.
- Spatial transcriptomics reveals microenvironmental heterogeneity in osteoarthritic subchondral bone.Nature communications · 2026Article
- Inhibition of EED enhances osteogenic differentiation and bone formation: a potential therapeutic strategy for osteogenesis imperfecta.JBMR plus · 2026Article
- OMICS Profiling Identifies Signatures of Senescence in Osteogenesis Imperfecta Osteoblasts Counteracted by 4-PBA.Journal of cellular and molecular medicine · 2026Article
- Current advances of bone homeostasis imbalance in the cause of hereditary metabolic bone diseases.EFORT open reviews · 2026Review
- 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
- LC3 and GABARAP independent autophagy of misfolded procollagen in mouse osteoblasts.Autophagy · 2025Article
- Failed Cellular Surveillance Enables Pathogenic Matrix Deposition in abioRxiv : the preprint server for biology · 2025Article
- Endoplasmic reticulum stress disrupts signaling via altered processing of transmembrane receptors.Cell communication and signaling : CCS · 2025Article
- Example of Intrafamilial Clinical Polymorphism in a Family with Osteogenesis Imperfecta.Genes · 2025Article
- The administration of exogenous HSP47 as a collagen-specific therapeutic approach.JCI insight · 2025Article
- Pleiotropic effects of a recessive Col1a2 mutation occurring in a mouse model of severe osteogenesis imperfecta.PloS one · 2025Article
- ER procollagen storage defect without coupled unfolded protein response drives precocious arthritis.Life science alliance · 2024Article
- The double whammy of ER-retention and dominant-negative effects in numerous autosomal dominant diseases: significance in disease mechanisms and therapy.Journal of biomedical science · 2024Review
- 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
- Loss of chaperone-mediated autophagy does not alter age-related bone loss in male mice.FASEB bioAdvances · 2024Article
- Designing collagens to shed light on the multi-scale structure-function mapping of matrix disorders.Matrix biology plus · 2024Review
- Altered Sox9 and FGF signaling gene expression in Aga2 OI mice negatively affects linear growth.JCI insight · 2023Article
- Bone Formation in 2D Culture of Primary Cells.JBMR plus · 2023Article
- Murine Animal Models in Osteogenesis Imperfecta: The Quest for Improving the Quality of Life.International journal of molecular sciences · 2022Review
2 more citing papers are in PubMed but not listed here.
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
Abstract
Glycine (Gly) substitutions in collagen Gly-X-Y repeats disrupt folding of type I procollagen triple helix and cause severe bone fragility and malformations (osteogenesis imperfecta [OI]). However, these mutations do not elicit the expected endoplasmic reticulum (ER) stress response, in contrast to other protein-folding diseases. Thus, it has remained unclear whether cell stress and osteoblast malfunction contribute to the bone pathology caused by Gly substitutions. Here we used a mouse with a Gly610 to cysteine (Cys) substitution in the procollagen α2(I) chain to show that misfolded procollagen accumulation in the ER leads to an unusual form of cell stress, which is neither a conventional unfolded protein response (UPR) nor ER overload. Despite pronounced ER dilation, there is no upregulation of binding immunoglobulin protein (BIP) expected in the UPR and no activation of NF-κB signaling expected in the ER overload. Altered expression of ER chaperones αB crystalline and HSP47, phosphorylation of EIF2α, activation of autophagy, upregulation of general stress response protein CHOP, and osteoblast malfunction reveal some other adaptive response to the ER disruption. We show how this response alters differentiation and function of osteoblasts in culture and in vivo. We demonstrate that bone matrix deposition by cultured osteoblasts is rescued by activation of misfolded procollagen autophagy, suggesting a new therapeutic strategy for OI. © 2016 American Society for Bone and Mineral Research.
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