ArticleJournal of cell science2013
Postnatal ablation of osteoblast Smad4 enhances proliferative responses to canonical Wnt signaling through interactions with β-catenin.
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 17 papers.
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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
17 citing papers in PubMed, 27 citations in OpenAlex.
- β-Catenin: A Key Molecule in Osteoblast Differentiation.Biomolecules · 2025Review
- BMP-2-Driven Osteogenesis: A Comparative Analysis of Porcine BMSCs and ASCs and the Role of TGF-β and FGF Signaling.Biology · 2025Article
- Signalling interaction between β-catenin and other signalling molecules during osteoarthritis development.Cell proliferation · 2024Review
- Wnt signaling: Essential roles in osteoblast differentiation, bone metabolism and therapeutic implications for bone and skeletal disorders.Genes & diseases · 2023Review
- The Smad4-MYO18A-PP1A complex regulates β-catenin phosphorylation and pemigatinib resistance by inhibiting PAK1 in cholangiocarcinoma.Cell death and differentiation · 2022Article
- SMAD4 contributes to chondrocyte and osteocyte development.Journal of cellular and molecular medicine · 2022Review
- Exercise improves bone formation by upregulating the Wnt3a/β-catenin signalling pathway in type 2 diabetic mice.Diabetology & metabolic syndrome · 2021Article
- Review
- Dynamic Expression Profiles of β-Catenin during Murine Cardiac Valve Development.Journal of cardiovascular development and disease · 2020Article
- The Role of Tantalum Nanoparticles in Bone Regeneration Involves the BMP2/Smad4/Runx2 Signaling Pathway.International journal of nanomedicine · 2020Article
- TGFβ-induced degradation of TRAF3 in mesenchymal progenitor cells causes age-related osteoporosis.Nature communications · 2019Article
- Signals in Stem Cell Differentiation on Fluorapatite-Modified Scaffolds.Journal of dental research · 2018Article
- Effects of miR-146a on the osteogenesis of adipose-derived mesenchymal stem cells and bone regeneration.Scientific reports · 2017Article
- Lrp5/β-Catenin Signaling Controls Lung Macrophage Differentiation and Inhibits Resolution of Fibrosis.American journal of respiratory cell and molecular biology · 2017Article
- Smad4 in osteoblasts exerts a differential impact on HSC fate depending on osteoblast maturation stage.Leukemia · 2016Article
- Smad4 controls bone homeostasis through regulation of osteoblast/osteocyte viability.Experimental & molecular medicine · 2016Article
- TGF-β and BMP signaling in osteoblast, skeletal development, and bone formation, homeostasis and disease.Bone research · 2016Review
Corrections and comments
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
Abstract
Canonical Wnt (cWnt) signaling through β-catenin regulates osteoblast proliferation and differentiation to enhance bone formation. We previously reported that osteogenic action of β-catenin is dependent on BMP signaling. Here, we further examined interactions between cWnt and BMP in bone. In osteoprogenitors stimulated with BMP2, β-catenin localizes to the nucleus, physically interacts with Smad4, and is recruited to DNA-binding transcription complexes containing Smad4, R-Smad1/5 and TCF4. Furthermore, Tcf/Lef-dependent transcription, Ccnd1 expression and proliferation all increase when Smad4, 1 or 5 levels are low, whereas TCF/Lef activities decrease when Smad4 expression is high. The ability of Smad4 to antagonize transcription of Ccnd1 is dependent on DNA-binding activity but Smad4-dependent transcription is not required. In mice, conditional deletion of Smad4 in osterix(+) cells increases mitosis of cells on trabecular bone surfaces as well as in primary osteoblast cultures from adult bone marrow and neonatal calvaria. By contrast, ablation of Smad4 delays differentiation and matrix mineralization by primary osteoblasts in response to Wnt3a, indicating that loss of Smad4 perturbs the balance between proliferation and differentiation in osteoprogenitors. We propose that Smad4 and Tcf/Lef transcription complexes compete for β-catenin, thus restraining cWnt-dependent proliferative signals while favoring the matrix synthesizing activity of osteoblasts.
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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.