ArticlePloS one2012
Synergistic inhibition of Wnt pathway by HIF-1α and osteoblast-specific transcription factor osterix (Osx) in osteoblasts.
Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed, 66 citations in OpenAlex.
- Molecular drivers of osteogenesis imperfecta: a cellular and extracellular collagen disease.Clinical science (London, England : 1979) · 2025Review
- Molecular crosstalk in SP7-mediated osteogenesis: Regulatory mechanisms and therapeutic potential.Osteoporosis and sarcopenia · 2025Review
- Ras-proximate-1 (RAP1): a prognosis and therapeutic target in the metastatic spread of breast cancer.Clinical & experimental metastasis · 2025Review
- WDR36 inhibits the osteogenic differentiation and migration of periodontal ligament stem cells.World journal of stem cells · 2025Article
- Hypoxia Promotes the Stemness of Mesangiogenic Progenitor Cells and Prevents Osteogenic but not Angiogenic Differentiation.Stem cell reviews and reports · 2024Article
- Differential but complementary roles of HIF-1α and HIF-2α in the regulation of bone homeostasis.Communications biology · 2024Article
- Cell signaling and transcriptional regulation of osteoblast lineage commitment, differentiation, bone formation, and homeostasis.Cell discovery · 2024Review
- The Bioactive Compounds ofPharmaceuticals (Basel, Switzerland) · 2024Article
- Hypoxia inducible factor-1α related mechanism and TCM intervention in process of early fracture healing.Chinese herbal medicines · 2024Review
- HIF-1α increases the osteogenic capacity of ADSCs by coupling angiogenesis and osteogenesis via the HIF-1α/VEGF/AKT/mTOR signaling pathway.Journal of nanobiotechnology · 2023Article
- Hypoxia Pathway in Osteoporosis: Laboratory Data for Clinical Prospects.International journal of environmental research and public health · 2023Review
- Bone marrow mesenchymal stem cell's exosomes as key nanoparticles in osteogenesis and bone regeneration: specific capacity based on cell type.Molecular biology reports · 2022Review
- Hypoxia-Inducible Factors Signaling in Osteogenesis and Skeletal Repair.International journal of molecular sciences · 2022Review
- Systematic review on the application of 3D-bioprinting technology in orthoregeneration: current achievements and open challenges.Journal of experimental orthopaedics · 2022Review
- Deciphering Obesity-Related Gene Clusters Unearths SOCS3 Immune Infiltrates and 5mC/m6A Modifiers in Ossification of Ligamentum Flavum Pathogenesis.Frontiers in endocrinology · 2022Article
- The Cellular Choreography of Osteoblast Angiotropism in Bone Development and Homeostasis.International journal of molecular sciences · 2021Review
- A functional map of genomic HIF1α-DNA complexes in the eye lens revealed through multiomics analysis.BMC genomics · 2021Article
- Effect of edaravone on pregnant mice and their developing fetuses subjected to placental ischemia.Reproductive biology and endocrinology : RB&E · 2021Article
- miR-145-5p suppresses osteogenic differentiation of adipose-derived stem cells by targeting semaphorin 3A.In vitro cellular & developmental biology. Animal · 2019Article
- Hypoxia Signaling in the Skeleton: Implications for Bone Health.Current osteoporosis reports · 2019Review
Corrections and comments
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Authors and funding
8 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Osterix (Osx) is an osteoblast-specific transcription factor required for osteoblast differentiation. Inhibition of Wnt pathway by Osx highlights the potential for feedback control mechanisms involved in bone formation. Hypoxia-inducible factor-1α (HIF-1α) is a master regulator of hypoxia. HIF-1α has been reported to couple angiogenesis to osteogenesis. Our recent study has demonstrated that Osx and HIF-1α cooperatively regulate VEGF expression in osteoblasts. Effects of hypoxia/HIF-1α on osteoblast proliferation and related mechanisms are not well understood. In this study, osteoblast growth under hypoxia was examined. We observed that osteoblast growth was inhibited under hypoxia. To explore possible mechanisms for hypoxia/HIF-1α to inhibit osteoblast proliferation, we tested the effect of hypoxia/HIF-1α on Wnt pathway. Quantitative RT-PCR results revealed that Wnt target genes such as cyclin D1 and c-Myc were downregulated under hypoxia while HIF-1α was upregulated. Treatment of desferrioxamine, a HIF-1α activator, led to further downregulation of expressions of cyclin D1 and c-Myc in osteoblasts. On the contrary, the inhibition of HIF-1α by siRNA in osteoblasts led to the expression increase of cyclin D1 and c-Myc. These data suggest that HIF-1α inhibits Wnt pathway in osteoblasts. To examine the effect of HIF-1α on Wnt pathway, HIF-1α was cotransfected with β-catenin along with Topflash reporter in transient transfection assay. Our results showed that HIF-1α inhibited β-catenin-induced Topflash reporter activity. Interestingly, a synergistic interplay was observed between Osx and HIF-1α in the inhibition of β-catenin-induced Topflash expression. Our findings indicate that Osx and HIF-1α cooperatively inhibit Wnt pathway. This study revealed additional new information of the cooperation between HIF-1α and Osx in osteoblasts.
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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.