ArticleJournal of cell science2013
Embryonic ablation of osteoblast Smad4 interrupts matrix synthesis in response to canonical Wnt signaling and causes an osteogenesis-imperfecta-like phenotype.
Article in Journal of cell science, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
27 citing papers in PubMed, 41 citations in OpenAlex.
- Intestinal Epithelial-like Cells Stimulated by a Functional Food Ingredient Promote Lysyl Oxidase (LOX) Expression in Osteoblast Precursor Cells via BMP-1 Secretion.International journal of molecular sciences · 2026Article
- lncTIMP3 promotes osteogenic differentiation of bone marrow mesenchymal stem cells via miR-214/Smad4 axis to relieve postmenopausal osteoporosis.Molecular biology reports · 2024Article
- Article
- Histone demethylase KDM7A regulates bone homeostasis through balancing osteoblast and osteoclast differentiation.Cell death & disease · 2024Article
- The roles and regulatory mechanisms of TGF-β and BMP signaling in bone and cartilage development, homeostasis and disease.Cell research · 2024Review
- Post-Transcriptional Regulatory Crosstalk between MicroRNAs and Canonical TGF-β/BMP Signalling Cascades on Osteoblast Lineage: A Comprehensive Review.International journal of molecular sciences · 2023Review
- Bone morphogenetic protein 4 is involved in cadmium-associated bone damage.Toxicological sciences : an official journal of the Society of Toxicology · 2023Article
- Lysyl oxidase regulation and protein aldehydes in the injured newborn lung.American journal of physiology. Lung cellular and molecular physiology · 2022Article
- SMAD4 contributes to chondrocyte and osteocyte development.Journal of cellular and molecular medicine · 2022Review
- Article
- From Stem Cells to Bone-Forming Cells.International journal of molecular sciences · 2021Review
- Lysyl Oxidase (LOX): Functional Contributions to Signaling Pathways.Biomolecules · 2020Review
- Lysyl oxidases: linking structures and immunity in the tumor microenvironment.Cancer immunology, immunotherapy : CII · 2020Review
- 5'-hydroxy Auraptene stimulates osteoblast differentiation of bone marrow-derived mesenchymal stem cells via a BMP-dependent mechanism.Journal of biomedical science · 2019Article
- TGFβ-induced degradation of TRAF3 in mesenchymal progenitor cells causes age-related osteoporosis.Nature communications · 2019Article
- GROWTH AND DEVELOPMENT SYMPOSIUM: STEM AND PROGENITOR CELLS IN ANIMAL GROWTH: The regulation of beef quality by resident progenitor cells1.Journal of animal science · 2019Article
- Reactivation of a developmentaleLife · 2019Article
- [Role of miR-144-3p and its target gene in regulating osteogenic differentiation of rat bone marrow mesenchymal stem cellsNan fang yi ke da xue xue bao = Journal of Southern Medical University · 2018Article
- Smad4 deficiency impairs chondrocyte hypertrophy via the Runx2 transcription factor in mouse skeletal development.The Journal of biological chemistry · 2018Article
- N-cadherin Regulation of Bone Growth and Homeostasis Is Osteolineage Stage-Specific.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2017Article
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
To examine interactions between bone morphogenic protein (BMP) and canonical Wnt signaling during skeletal growth, we ablated Smad4, a key component of the TGF-β-BMP pathway, in Osx1(+) cells in mice. We show that loss of Smad4 causes stunted growth, spontaneous fractures and a combination of features seen in osteogenesis imperfecta, cleidocranial dysplasia and Wnt-deficiency syndromes. Bones of Smad4 mutant mice exhibited markers of fully differentiated osteoblasts but lacked multiple collagen-processing enzymes, including lysyl oxidase (Lox), a BMP2-responsive gene regulated by Smad4 and Runx2. Accordingly, the collagen matrix in Smad4 mutants was disorganized, but also hypomineralized. Primary osteoblasts from these mutants did not mineralize in vitro in the presence of BMP2 or Wnt3a, and Smad4 mutant mice failed to accrue new bone following systemic inhibition of the Dickkopf homolog Dkk1. Consistent with impaired biological responses to canonical Wnt, ablation of Smad4 causes cleavage of β-catenin and depletion of the low density lipoprotein receptor Lrp5, subsequent to increased caspase-3 activity and apoptosis. In summary, Smad4 regulates maturation of skeletal collagen and osteoblast survival, and is required for matrix-forming responses to both BMP2 and canonical Wnt.
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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.