ArticleThe Journal of biological chemistry2012
Orphan nuclear receptor chicken ovalbumin upstream promoter-transcription factor II (COUP-TFII) protein negatively regulates bone morphogenetic protein 2-induced osteoblast differentiation through suppressing runt-related gene 2 (Runx2) activity.
Article in The Journal of biological chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 29 citations in OpenAlex.
- SCFSignal transduction and targeted therapy · 2026Article
- Data-driven inference of Boolean networks from transcriptomes to predict cellular differentiation and reprogramming.NPJ systems biology and applications · 2025Article
- Localized COUP-TFII pDNA Delivery Modulates Stem/Progenitor Cell Differentiation to Enhance Endothelialization and Inhibit Calcification of Decellularized Allografts.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Cell signaling and transcriptional regulation of osteoblast lineage commitment, differentiation, bone formation, and homeostasis.Cell discovery · 2024Review
- Case Report and Review of the Literature: Congenital Diaphragmatic Hernia and Craniosynostosis, a Coincidence or Common Cause?Frontiers in pediatrics · 2021Article
- COUP-TFII in Health and Disease.Cells · 2019Review
- Overview of the structure-based non-genomic effects of the nuclear receptor RXRα.Cellular & molecular biology letters · 2018Review
- COUP-TFII is required for morphogenesis of the neural crest-derived tympanic ring.Scientific reports · 2017Article
- Strain differences in the attenuation of bone accrual in a young growing mouse model of insulin resistance.Journal of bone and mineral metabolism · 2016Article
- A Member of the Nuclear Receptor Superfamily, Designated as NR2F2, Supports the Self-Renewal Capacity and Pluripotency of Human Bone Marrow-Derived Mesenchymal Stem Cells.Stem cells international · 2016Article
- FGF2 Stimulates COUP-TFII Expression via the MEK1/2 Pathway to Inhibit Osteoblast Differentiation in C3H10T1/2 Cells.PloS one · 2016Article
- MicroRNA-194 reciprocally stimulates osteogenesis and inhibits adipogenesis via regulating COUP-TFII expression.Cell death & disease · 2014Article
- Mitogen-activated protein kinase (MAPK)-regulated interactions between Osterix and Runx2 are critical for the transcriptional osteogenic program.The Journal of biological chemistry · 2014Article
- COUP-TFII regulates metastasis of colorectal adenocarcinoma cells by modulating Snail1.British journal of cancer · 2014Article
- Orphan nuclear receptor NR2F6 acts as an essential gatekeeper of Th17 CD4+ T cell effector functions.Cell communication and signaling : CCS · 2014Review
- Regulatory potential of COUP-TFs in development: stem/progenitor cells.Seminars in cell & developmental biology · 2013Review
- Transcriptional regulatory cascades in Runx2-dependent bone development.Tissue engineering. Part B, Reviews · 2013Review
- Clinical significance of RUNX2 expression in patients with nonsmall cell lung cancer: a 5-year follow-up study.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2013Article
- Multiple roles of COUP-TFII in cancer initiation and progression.Journal of molecular endocrinology · 2012Review
- Overexpression of runt-related transcription factor-2 is associated with advanced tumor progression and poor prognosis in epithelial ovarian cancer.Journal of biomedicine & biotechnology · 2012Article
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Chicken ovalbumin upstream promoter-transcription factor II (COUP-TFII) is an orphan nuclear receptor of the steroid-thyroid hormone receptor superfamily. COUP-TFII is widely expressed in multiple tissues and organs throughout embryonic development and has been shown to regulate cellular growth, differentiation, and organ development. However, the role of COUP-TFII in osteoblast differentiation has not been systematically evaluated. In the present study, COUP-TFII was strongly expressed in multipotential mesenchymal cells, and the endogenous expression level decreased during osteoblast differentiation. Overexpression of COUP-TFII inhibited bone morphogenetic protein 2 (BMP2)-induced osteoblastic gene expression. The results of alkaline phosphatase, Alizarin Red staining, and osteocalcin production assay showed that COUP-TFII overexpression blocks BMP2-induced osteoblast differentiation. In contrast, the down-regulation of COUP-TFII synergistically induced the expression of BMP2-induced osteoblastic genes and osteoblast differentiation. Furthermore, the immunoprecipitation assay showed that COUP-TFII and Runx2 physically interacted and COUP-TFII significantly impaired the Runx2-dependent activation of the osteocalcin promoter. From the ChIP assay, we found that COUP-TFII repressed DNA binding of Runx2 to the osteocalcin gene, whereas Runx2 inhibited COUP-TFII expression via direct binding to the COUP-TFII promoter. Taken together, these findings demonstrate that COUP-TFII negatively regulates osteoblast differentiation via interaction with Runx2, and during the differentiation state, BMP2-induced Runx2 represses COUP-TFII expression and promotes osteoblast differentiation.
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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.