ArticleInternational journal of oral science2019
Overexpression of Dlx2 enhances osteogenic differentiation of BMSCs and MC3T3-E1 cells via direct upregulation of Osteocalcin and Alp.
Article in International journal of oral science, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.
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Who cites it
48 citing papers in PubMed, 103 citations in OpenAlex.
- Inhibition of ELK1 promotes osteogenic differentiation of periodontal ligament stem cells by reducing ubiquitin-mediated degradation of DLX2.Journal of molecular medicine (Berlin, Germany) · 2026Article
- Genetic and genomic insights into morphological defects in nellore cattle: a comprehensive review.Tropical animal health and production · 2026Review
- Gut‑bone metabolites: SCFAs, polyamines and microbial metabolomics in osteoporosis risk and therapy (Review).International journal of molecular medicine · 2026Review
- Salvianolic acid B mitigates senescence and promotes osteogenesis of senescent bone marrow mesenchymal stem cells via the PI3K/AKT pathway.Biochemistry and biophysics reports · 2026Article
- Application Strategies of Bone Marrow Mesenchymal Stromal Cells in Bone-Related Diseases.Cell proliferation · 2026Review
- Hydrogel scaffold encapsulating MSC-Exos and ZIF-8 promotes bone regeneration via coordinating osteogenesis and immunomodulation.Bioactive materials · 2025Article
- CH02 peptide-stimulated periodontal ligament cells enhance periodontal defect repair in rats.BMC oral health · 2025Article
- SENP3 alleviates osteoporosis via promoting SIRT3 transcription through the increase of DLX2 stability via SUMO2/3.Cell biology and toxicology · 2025Article
- Geraniin Promotes Osteoblast Proliferation, Bone Formation, and Autophagy by Regulating the PI3K/Akt/mTOR Cascade to Improve Glucocorticoid-Induced Osteoporosis.Calcified tissue international · 2025Article
- Knockdown of IER3 Promotes Osteogenic Differentiation of Human Mesenchymal Stem Cells.Biomedicines · 2025Article
- A galactose-tethered tetraphenylethene prodrug mediated apoptosis of senescent cells for osteoporosis treatment.Science advances · 2025Article
- Specnuezhenide Alleviates Senile Osteoporosis by Activating TGR5/FXR Signaling in Bone Marrow Mesenchymal Stem Cells and RANKL-Induced Osteoclasts.Drug design, development and therapy · 2025Article
- Salidroside Improves Periodontitis by Mitigating Inflammatory Reactions and Enhancing Osteogenic Differentiation of Human Periodontal Ligament Stem Cells.Drug design, development and therapy · 2025Article
- Decoding dental mesenchymal stem cells diversity: single-cell transcriptomics maps heterogeneity in molar development.Frontiers in cell and developmental biology · 2025Review
- Analysis of the CPZ/Wnt4 osteogenic pathway for high-bonding-strength composite-coated magnesium scaffolds through transcriptomics.Materials today. Bio · 2024Article
- Novel FeInternational journal of molecular sciences · 2024Article
- Cell-microsphere based living microhybrids for osteogenesis regulating to boosting biomineralization.Regenerative biomaterials · 2024Article
- Mesenchymal stem cells-derived extracellular vesicles protect against oxidative stress-induced xenogeneic biological root injury via adaptive regulation of the PI3K/Akt/NRF2 pathway.Journal of nanobiotechnology · 2023Article
- Reactive Oxygen Species Scavenging Hydrogel Regulates Stem Cell Behavior and Promotes Bone Healing in Osteoporosis.Tissue engineering and regenerative medicine · 2023Article
- Biodegradation and Cell Behavior of a Mg-Based Composite with Mesoporous Bioglass.Materials (Basel, Switzerland) · 2023Article
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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
Genetic studies have revealed a critical role of Distal-homeobox (Dlx) genes in bone formation, and our previous study showed that Dlx2 overexpressing in neural crest cells leads to profound abnormalities of the craniofacial tissues. The aim of this study was to investigate the role and the underlying molecular mechanisms of Dlx2 in osteogenic differentiation of mouse bone marrow stromal cells (BMSCs) and pre-osteoblast MC3T3-E1 cells. Initially, we observed upregulation of Dlx2 during the early osteogenesis in BMSCs and MC3T3-E1 cells. Moreover, Dlx2 overexpression enhanced alkaline phosphatase (ALP) activity and extracellular matrix mineralization in BMSCs and MC3T3-E1 cell line. In addition, micro-CT of implanted tissues in nude mice confirmed that Dlx2 overexpression in BMSCs promoted bone formation in vivo. Unexpectedly, Dlx2 overexpression had little impact on the expression level of the pivotal osteogenic transcription factors Runx2, Dlx5, Msx2, and Osterix, but led to upregulation of Alp and Osteocalcin (OCN), both of which play critical roles in promoting osteoblast maturation. Importantly, luciferase analysis showed that Dlx2 overexpression stimulated both OCN and Alp promoter activity. Through chromatin-immunoprecipitation assay and site-directed mutagenesis analysis, we provide molecular evidence that Dlx2 transactivates OCN and Alp expression by directly binding to the Dlx2-response cis-acting elements in the promoter of the two genes. Based on these findings, we demonstrate that Dlx2 overexpression enhances osteogenic differentiation in vitro and accelerates bone formation in vivo via direct upregulation of the OCN and Alp gene, suggesting that Dlx2 plays a crucial role in osteogenic differentiation and bone formation.
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