ArticleMolecular therapy : the journal of the American Society of Gene Therapy2024
Nr4a1 enhances Wnt4 transcription to promote mesenchymal stem cell osteogenesis and alleviates inflammation-inhibited bone regeneration.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 24 citations in OpenAlex.
- Review
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- Targeted antibacterial and mesenchymal stem cell-modulatory hydrogel for periodontitis treatment.Materials today. Bio · 2026Article
- Immunosenescence and Bone Homeostasis: From Mechanisms of Homeostasis Disruption to Therapeutic Opportunities in Age-Related Skeletal Disorders.International journal of molecular sciences · 2026Review
- Nur77 Is Associated With Polyfunctional Properties in Virus-Specific Human CD8European journal of immunology · 2026Article
- Application Strategies of Bone Marrow Mesenchymal Stromal Cells in Bone-Related Diseases.Cell proliferation · 2026Review
- The Sirt2-Nur77 axis regulates muscle stem cell quiescence and senescence via epigenetic-metabolic synergy.Cell death & disease · 2026Article
- Estrogen upregulates NR4A1 to counter TGF beta induced pulmonary fibrosis therapeutic insights for IPF.iScience · 2026Article
- Trifunctional synergistically designed 3D-Printed bone scaffold for infectious bone defect therapy: design strategy and clinical translation outlook.Frontiers in bioengineering and biotechnology · 2026Review
- Bioaugmented osteosynthesis: precise monitoring and intervention of the bone healing microenvironment.Bone research · 2025Article
- Genomic structural equation modeling uncovers novel risk loci for bone metabolic disorders: cross-tissue genetic mechanisms and bone-brain axis regulation.BMC musculoskeletal disorders · 2025Article
- Baicalein attenuates ovalbumin-induced allergic rhinitis through the activation of nuclear receptor subfamily 4 group a member 1.Immunologic research · 2025Article
- Exercise ameliorates osteopenia in mice via intestinal microbial-mediated bile acid metabolism pathway.Theranostics · 2025Article
- Endothelial cell-modified BMSC-GT/PCL nanofiber membrane sheet constructs promote bone tissue regeneration.Frontiers in bioengineering and biotechnology · 2025Article
- Mechanisms and therapeutic strategies linking mesenchymal stem cells senescence to osteoporosis.Frontiers in endocrinology · 2025Review
- Combined bone marrow mesenchymal stem cell-derived nanovesicles and low-level laser therapy potentiate proliferation and osteogenesis of bone marrow mesenchymal stem cells.Frontiers in bioengineering and biotechnology · 2025Article
- Spatiotemporal application of small molecules in fracture healing.Biomaterials translational · 2025Review
- Bone-protective effects of neutralizing angiopoietin-like protein 4 monoclonal antibody in rheumatoid arthritis.Molecular therapy : the journal of the American Society of Gene Therapy · 2024Article
Corrections and comments
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Authors and funding
12 authors at 6 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Intense inflammatory response impairs bone marrow mesenchymal stem cell (BMSC)-mediated bone regeneration, with transforming growth factor (TGF)-β1 being the most highly expressed cytokine. However, how to find effective and safe means to improve bone formation impaired by excessive TGF-β1 remains unclear. In this study, we found that the expression of orphan nuclear receptor Nr4a1, an endogenous repressor of TGF-β1, was suppressed directly by TGF-β1-induced Smad3 and indirectly by Hdac4, respectively. Importantly, Nr4a1 overexpression promoted BMSC osteogenesis and reversed TGF-β1-mediated osteogenic inhibition and pro-fibrotic effects. Transcriptomic and histologic analyses confirmed that upregulation of Nr4a1 increased the transcription of Wnt family member 4 (Wnt4) and activated Wnt pathway. Mechanistically, Nr4a1 bound to the promoter of Wnt4 and regulated its expression, thereby enhancing the osteogenic capacity of BMSCs. Moreover, treatment with Nr4a1 gene therapy or Nr4a1 agonist Csn-B could promote ectopic bone formation, defect repair, and fracture healing. Finally, we demonstrated the correlation of NR4A1 with osteogenesis and the activation of the WNT4/β-catenin pathway in human BMSCs and fracture samples. Taken together, these findings uncover the critical role of Nr4a1 in bone formation and alleviation of inflammation-induced bone regeneration disorders, and suggest that Nr4a1 has the potential to be a therapeutic target for accelerating bone healing.
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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 Socratic graph.