ArticleCell death and differentiation2017
p53 inhibits SP7/Osterix activity in the transcriptional program of osteoblast differentiation.
Article in Cell death and differentiation, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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Who cites it
39 citing papers in PubMed, 60 citations in OpenAlex.
- The MDM2-p53 Axis in Osteosarcoma: Current Understanding of Regulatory Mechanisms and Targeted Therapeutic Strategies.Pharmaceuticals (Basel, Switzerland) · 2026Review
- FBXO5 alleviates apical periodontitis by facilitating TP53 protein degradation.International dental journal · 2026Article
- MiR-376a-3p inhibits bone repair by regulating osteoblastic differentiation.Journal of orthopaedic surgery and research · 2025Article
- Molecular crosstalk in SP7-mediated osteogenesis: Regulatory mechanisms and therapeutic potential.Osteoporosis and sarcopenia · 2025Review
- Nuclear farnesoid X receptor protects against bone loss by driving osteoblast differentiation through stabilizing RUNX2.Bone research · 2025Article
- Fam102a translocates Runx2 and Rbpjl to facilitate Osterix expression and bone formation.Nature communications · 2025Article
- Article
- Mesenchymal stem cells under epigenetic control - the role of epigenetic machinery in fate decision and functional properties.Cell death & disease · 2023Review
- BMP-9 Improves the Osteogenic Differentiation Ability over BMP-2 through p53 Signaling In Vitro in Human Periosteum-Derived Cells.International journal of molecular sciences · 2023Article
- The Molecular Regulatory Mechanism in Multipotency and Differentiation of Wharton's Jelly Stem Cells.International journal of molecular sciences · 2023Review
- Aged mesenchymal stem cells and inflammation: from pathology to potential therapeutic strategies.Biology direct · 2023Review
- Japanese medaka Olpax6.1 mutant as a potential model for spondylo-ocular syndrome.Functional & integrative genomics · 2023Article
- P53 negatively regulates the osteogenic differentiation in jaw bone marrow MSCs derived from diabetic osteoporosis.Heliyon · 2023Article
- SP7: from Bone Development to Skeletal Disease.Current osteoporosis reports · 2023Review
- A Review of Signaling Transduction Mechanisms in Osteoclastogenesis Regulation by Autophagy, Inflammation, and Immunity.International journal of molecular sciences · 2022Review
- CK1α/RUNX2 Axis in the Bone Marrow Microenvironment: A Novel Therapeutic Target in Multiple Myeloma.Cancers · 2022Article
- Sp7 Action in the Skeleton: Its Mode of Action, Functions, and Relevance to Skeletal Diseases.International journal of molecular sciences · 2022Review
- p53 deficiency promotes bone regeneration by functional regulation of mesenchymal stromal cells and osteoblasts.Journal of bone and mineral metabolism · 2022Article
- Enamel matrix derivative (EMD) enhances the osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs).Bioengineered · 2021Article
- STAT3 is critical for skeletal development and bone homeostasis by regulating osteogenesis.Nature communications · 2021Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Osteoblast differentiation is achieved by activating a transcriptional network in which Dlx5, Runx2 and Osx/SP7 have fundamental roles. The tumour suppressor p53 exerts a repressive effect on bone development and remodelling through an unknown mechanism that inhibits the osteoblast differentiation programme. Here we report a physical and functional interaction between Osx and p53 gene products. Physical interaction was found between overexpressed proteins and involved a region adjacent to the OSX zinc fingers and the DNA-binding domain of p53. This interaction results in a p53-mediated repression of OSX transcriptional activity leading to a downregulation of the osteogenic programme. Moreover, we show that p53 is also able to repress key osteoblastic genes in Runx2-deficient osteoblasts. The ability of p53 to suppress osteogenesis is independent of its DNA recognition ability but requires a native conformation of p53, as a conformational missense mutant failed to inhibit OSX. Our data further demonstrates that p53 inhibits OSX binding to their responsive Sp1/GC-rich sites in the promoters of their osteogenic target genes, such as IBSP or COL1A1. Moreover, p53 interaction to OSX sequesters OSX from binding to DLX5. This competition blocks the ability of OSX to act as a cofactor of DLX5 to activate homeodomain-containing promoters. Altogether, our data support a model wherein p53 represses OSX-DNA binding and DLX5-OSX interaction, and thereby deregulates the osteogenic transcriptional network. This mechanism might have relevant roles in bone pathologies associated to osteosarcomas and ageing.
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