ArticleMolecular and cellular biology2004
Dlx3 transcriptional regulation of osteoblast differentiation: temporal recruitment of Msx2, Dlx3, and Dlx5 homeodomain proteins to chromatin of the osteocalcin gene.
Article in Molecular and cellular biology, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 120 papers.
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Who cites it
120 citing papers in PubMed, 284 citations in OpenAlex.
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- Cell signaling and transcriptional regulation of osteoblast lineage commitment, differentiation, bone formation, and homeostasis.Cell discovery · 2024Review
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- Application of mesenchymal stem cell sheet for regeneration of craniomaxillofacial bone defects.Stem cell research & therapy · 2023Review
- A shared genetic contribution to osteoarthritis and COVID-19 outcomes: a large-scale genome-wide cross-trait analysis.Frontiers in immunology · 2023Article
- Enhanced osteogenesis of human urine-derived stem cells by direct delivery of 30Kc19α-Lin28A protein.Frontiers in bioengineering and biotechnology · 2023Article
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- Transcriptome Analysis Reveals Modulation of Human Stem Cells from the Apical Papilla by Species Associated with Dental Root Canal Infection.International journal of molecular sciences · 2022Article
- CRISPR/Cas9-mediated deletion of Fam83h induces defective tooth mineralization and hair development in rabbits.Journal of cellular and molecular medicine · 2022Article
- Review
- Salt Dependence of DNA Binding Activity of Human Transcription Factor Dlx3.International journal of molecular sciences · 2022Article
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- Mechanisms during Osteogenic Differentiation in Human Dental Follicle Cells.International journal of molecular sciences · 2022Review
- Sp7 Action in the Skeleton: Its Mode of Action, Functions, and Relevance to Skeletal Diseases.International journal of molecular sciences · 2022Review
- Effect of Cold Atmospheric Plasma (CAP) on Osteogenic Differentiation Potential of Human Osteoblasts.International journal of molecular sciences · 2022Article
- MiR-149-3p can improve the osteogenic differentiation of human adipose-derived stem cells via targeting AKT1.The Kaohsiung journal of medical sciences · 2021Article
60 more citing papers are in PubMed but not listed here.
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Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
Abstract
Genetic studies show that Msx2 and Dlx5 homeodomain (HD) proteins support skeletal development, but null mutation of the closely related Dlx3 gene results in early embryonic lethality. Here we find that expression of Dlx3 in the mouse embryo is associated with new bone formation and regulation of osteoblast differentiation. Dlx3 is expressed in osteoblasts, and overexpression of Dlx3 in osteoprogenitor cells promotes, while specific knock-down of Dlx3 by RNA interference inhibits, induction of osteogenic markers. We characterized gene regulation by Dlx3 in relation to that of Msx2 and Dlx5 during osteoblast differentiation. Chromatin immunoprecipitation assays revealed a molecular switch in HD protein association with the bone-specific osteocalcin (OC) gene. The transcriptionally repressed OC gene was occupied by Msx2 in proliferating osteoblasts, while Dlx3, Dlx5, and Runx2 were recruited postproliferatively to initiate transcription. Dlx5 occupancy increased over Dlx3 in mature osteoblasts at the mineralization stage of differentiation, coincident with increased RNA polymerase II occupancy. Dlx3 protein-DNA interactions stimulated OC promoter activity, while Dlx3-Runx2 protein-protein interaction reduced Runx2-mediated transcription. Deletion analysis showed that the Dlx3 interacting domain of Runx2 is from amino acids 376 to 432, which also include the transcriptionally active subnuclear targeting sequence (376 to 432). Thus, we provide cellular and molecular evidence for Dlx3 in regulating osteoprogenitor cell differentiation and for both positive and negative regulation of gene transcription. We propose that multiple HD proteins in osteoblasts constitute a regulatory network that mediates development of the bone phenotype through the sequential association of distinct HD proteins with promoter regulatory elements.
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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 OpenQuestion graph.