ArticleThe Journal of biological chemistry2012
Runx2 protein stabilizes hypoxia-inducible factor-1α through competition with von Hippel-Lindau protein (pVHL) and stimulates angiogenesis in growth plate hypertrophic chondrocytes.
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 52 papers.
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Who cites it
52 citing papers in PubMed, 97 citations in OpenAlex.
- Genome-wide DNA methylation changes after 24 hours at high altitude.Environmental epigenetics · 2026Article
- Overexpression of RUNX2 promotes breast cancer multi-organ metastasis through stabilizing c-Myc.Cell death & disease · 2025Article
- Molecular Crosstalk Between RUNX2 and HIF-1α in Osteosarcoma: Implications for Angiogenesis, Metastasis, and Therapy Resistance.International journal of molecular sciences · 2025Review
- Hydrogels with programmed spatiotemporal mechanical cues for stem cell-assisted bone regeneration.Nature communications · 2025Article
- Foxp1 suppresses cortical angiogenesis and attenuates HIF-1alpha signaling to promote neural progenitor cell maintenance.EMBO reports · 2024Article
- Article
- Mesenchymal stem cell-derived exosomes enriched with miR-218 reduce the epithelial-mesenchymal transition and angiogenesis in triple-negative breast cancer cells.European journal of medical research · 2023Article
- GRP78 promotes the osteogenic and angiogenic response in periodontal ligament stem cells.European cells & materials · 2023Article
- The role of chondrocyte-to-osteoblast trans-differentiation in fetal bone dysplasia of mice caused by prenatal exposure to dexamethasone.Frontiers in pharmacology · 2023Article
- HIF-1α upregulation exerts the antagonistic effect against angiogenesis inhibition in manganese deficiency-induced tibial dyschondroplasia of broiler chicks.Veterinary research communications · 2022Article
- Review
- Review
- Pro-Calcific Environment Impairs Ischaemia-Driven Angiogenesis.International journal of molecular sciences · 2022Article
- Uremic Toxin Lanthionine Induces Endothelial Cell Mineralization In Vitro.Biomedicines · 2022Article
- HIF-1α in Osteoarthritis: From Pathogenesis to Therapeutic Implications.Frontiers in pharmacology · 2022Review
- Endothelial PPARδ facilitates the post-ischemic vascular repair through interaction with HIF1α.Theranostics · 2022Article
- A Functional Network Model of the Metastasis Suppressor PEBP1/RKIP and Its Regulators in Breast Cancer Cells.Cancers · 2021Article
- Runt related transcription factor-1 plays a central role in vessel co-option of colorectal cancer liver metastases.Communications biology · 2021Article
- miR-204: Molecular Regulation and Role in Cardiovascular and Renal Diseases.Hypertension (Dallas, Tex. : 1979) · 2021Review
- BMSC-Exosomes Carry Mutant HIF-1α for Improving Angiogenesis and Osteogenesis in Critical-Sized Calvarial Defects.Frontiers in bioengineering and biotechnology · 2020Article
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The regulation of hypoxia-inducible factor-1α (HIF-1α) during endochondral bone formation is not fully understood. Here, we investigated the cross-talk between HIF-1α and Runt-related transcription factor 2 (Runx2) in the growth plate. Runx2 caused the accumulation of HIF-1α protein in ATDC5 chondrocytes and HEK293 cells under normoxic conditions. Runx2 also increased the nuclear translocation of HIF-1α when coexpressed in HEK293 cells and interacted with HIF-1α at the oxygen-dependent degradation domain (ODDD). In addition, Runx2 competed with von Hippel-Lindau tumor suppressor protein by directly binding to ODDD-HIF-1α and significantly inhibited the ubiquitination of HIF-1α, even though Runx2 did not change the hydroxylation status of HIF-1α. Furthermore, overexpression of Runx2 resulted in the significant enhancement of vascular endothelial growth factor (VEGF) promoter reporter activity and protein secretion. Runx2 significantly increased angiogenic activity in human umbilical vein endothelial cells in vitro. In wild-type mice, HIF-1α and Runx2 were colocalized in hypertrophic chondrocytes in which the cluster of differentiation 31 (CD31) protein was expressed at embryonic day 15.5 (E15.5). In contrast, the expression of HIF-1α was markedly reduced in areas of CD31 expression in Runx2(-/-) mice. These results suggest that Runx2 stabilizes HIF-1α by binding to ODDD to block the interaction between von Hippel-Lindau protein and HIF-1α. In conclusion, Runx2, HIF-1α, and VEGF may regulate vascular angiogenesis spatially and temporally in the hypertrophic zone of the growth plate during endochondral bone formation.
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