ArticleThe Journal of biological chemistry2014
Mitogen-activated protein kinase (MAPK)-regulated interactions between Osterix and Runx2 are critical for the transcriptional osteogenic program.
Article in The Journal of biological chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 74 papers.
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Who cites it
74 citing papers in PubMed, 132 citations in OpenAlex.
- Reprogramming bone homeostasis: The recoupling-oriented framework of bidirectional regulation strategies for osteoporosis.iScience · 2026Review
- SATB1 regulates the osteogenic differentiation of PDLSCs via HDAC1 mediated non-histone protein deacetylation and ubiquitination mechanism and through p38 MAPK pathway under hydrogen peroxide-induced senescent conditions.Stem cell research & therapy · 2026Article
- The role of bioactive molecules in enhancing bone healing in oral and maxillofacial surgery: a review of current approaches and future directions.Oral and maxillofacial surgery · 2026Review
- Long-term enoxaparin use and osteoporosis risk: a real-world cohort study with integrative computational and network toxicology approaches.Journal of translational medicine · 2026Article
- Propolis nanoemulsion and mesenchymal stem cell conditioned medium promote osteoblastogenesis against lipopolysaccharide-induced osteolysis in hyperglycemic rats.Scientific reports · 2026Article
- Bioglass-Reinforced Spongin-Like Collagen Scaffolds for Osteoporotic Bone Tissue Engineering.ACS omega · 2026Article
- Bone Marrow Mesenchymal Stromal Cell Osteogenesis is driven by Paracrine signals from Regulatory T Cell.Stem cell reviews and reports · 2026Article
- Genetic Engineering of Umbilical Cord-Derived Mesenchymal Stem Cells to Enhance BMP-2 Secretion via Signal Peptide Optimization.Biomedicines · 2025Article
- Review
- Propofol-induced osteogenic differentiation in dental pulp stem cells: Modulation of MAPK signaling under inflammatory conditions.Journal of dental sciences · 2025Article
- Advancing Scaffold Architecture for Bone Tissue Engineering: A Comparative Study of 3D-Printed β-TCP Constructs in Dynamic Culture with pBMSC.Journal of functional biomaterials · 2025Article
- Molecular Determinants of Bone Plasticity Regeneration After Trauma: Forensic Consequences.International journal of molecular sciences · 2025Review
- Gene Expression Profiling and Phenotypic Characterization of Circulating Tumor Cells Derived from a Murine Osteosarcoma Model.Cancers · 2025Article
- The proneural transcription factor Atoh1 promotes odontogenic differentiation in human dental pulp stem cells (DPSCs).BMC molecular and cell biology · 2025Article
- Bone development by Hedgehog and Wnt signaling, Runx2, and Sp7.Journal of bone and mineral metabolism · 2025Review
- Review
- The IFITM5 mutation in osteogenesis imperfecta type V is associated with an ERK/SOX9-dependent osteoprogenitor differentiation defect.The Journal of clinical investigation · 2024Article
- Osteogenic Differentiation Potential of iMSCs on GelMA-BG-MWCNT Nanocomposite Hydrogels.Biomimetics (Basel, Switzerland) · 2024Article
- Involvement of RAMP1/p38MAPK signaling pathway in osteoblast differentiation in response to mechanical stimulation: a preliminary study.Journal of orthopaedic surgery and research · 2024Article
- ATP6AP2, a regulator of LRP6/β-catenin protein trafficking, promotes Wnt/β-catenin signaling and bone formation in a cell type dependent manner.Bone research · 2024Article
14 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The transcription factors Runx2 and Osx (Osterix) are required for osteoblast differentiation and bone formation. Runx2 expression occurs at early stages of osteochondroprogenitor determination, followed by Osx induction during osteoblast maturation. We demonstrate that coexpression of Osx and Runx2 leads to cooperative induction of expression of the osteogenic genes Col1a1, Fmod, and Ibsp. Functional interaction of Osx and Runx2 in the regulation of these promoters is mediated by enhancer regions with adjacent Sp1 and Runx2 DNA-binding sites. These enhancers allow formation of a cooperative transcriptional complex, mediated by the binding of Osx and Runx2 to their specific DNA promoter sequences and by the protein-protein interactions between them. We also identified the domains involved in the interaction between Osx and Runx2. These regions contain the amino acids in Osx and Runx2 known to be phosphorylated by p38 and ERK MAPKs. Inhibition of p38 and ERK kinase activities or mutation of their known phosphorylation sites in Osx or Runx2 strongly disrupts their physical interaction and cooperative transcriptional effects. Altogether, our results provide a molecular description of a mechanism for Osx and Runx2 transcriptional cooperation that is subject to further regulation by MAPK-activating signals during osteogenesis.
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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.