ArticleStem cell research & therapy2020
Hypoxia alleviates dexamethasone-induced inhibition of angiogenesis in cocultures of HUVECs and rBMSCs via HIF-1α.
Article in Stem cell research & therapy, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 55 citations in OpenAlex.
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- The Role of miRNA-21 in the Metastasis of Hepatocellular Carcinoma as a Therapeutic Target.International journal of hematology-oncology and stem cell research · 2026Review
- Crosstalk between endothelial cells and osteoblasts stimulates ALP via Notch signaling and RANKL/OPG ratio independently of Notch signaling in vitro.Cellular & molecular biology letters · 2025Article
- Co-Culture Approaches in Cartilage and Bone Tissue Regeneration.International journal of molecular sciences · 2025Review
- Enhanced osteogenic and angiogenic capabilities of adipose-derived stem cells in fish collagen scaffolds for treatment of femoral head osteonecrosis.Scientific reports · 2025Article
- Plasmolipin deficiency is essential for HUVECs survival under hypoxic conditions.Cell death discovery · 2025Article
- Notch1 signaling regulates Sox9 and VEGFA expression and governs BMP2-induced endochondral ossification of mesenchymal stem cells.Genes & diseases · 2025Article
- Study on the mechanism of plant metabolites to intervene oxidative stress in diabetic retinopathy.Frontiers in pharmacology · 2025Review
- Diabetes current and future translatable therapies.Endocrine · 2024Review
- Posttranscriptional Modification to Modulate Progenitor Differentiation on Heterotypic Spheroids.Tissue engineering. Part A · 2024Article
- Article
- The Role of HIF-1α in Bone Regeneration: A New Direction and Challenge in Bone Tissue Engineering.International journal of molecular sciences · 2023Review
- Yth mInternational journal of molecular sciences · 2023Article
- Identification of a tsRNA Contributor to Impaired Diabetic Wound Healing via High Glucose-Induced Endothelial Dysfunction.Diabetes, metabolic syndrome and obesity : targets and therapy · 2023Article
- Review
- In Vitro Angiogenesis Inhibition and Endothelial Cell Growth and Morphology.International journal of molecular sciences · 2022Article
- A single-cell transcriptome of mesenchymal stromal cells to fabricate bioactive hydroxyapatite materials for bone regeneration.Bioactive materials · 2022Article
- A Composite Deferoxamine/Black Phosphorus Nanosheet/Gelatin Hydrogel Scaffold for Ischemic Tibial Bone Repair.International journal of nanomedicine · 2022Article
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9 authors at 1 institution in 1 country.
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No grant is acknowledged in the PubMed record.
Abstract
BACKGROUND AND
aimInadequate vascularization is a challenge in bone tissue engineering because internal cells are prone to necrosis due to a lack of nutrient supply. Rat bone marrow-derived mesenchymal stem cells (rBMSCs) and human umbilical vein endothelial cells (HUVECs) were cocultured to construct prevascularized bone tissue in osteogenic induction medium (OIM) in vitro. The angiogenic capacity of HUVECs was limited in the coculture system. In this study, the effects of the components in the medium on HUVEC angiogenesis were analyzed.
methodsThe coculture system was established in OIM. Alizarin red staining and alkaline phosphatase staining were used to assess the osteogenic ability of MSCs. A Matrigel tube assay was used to assess the angiogenic ability of HUVECs in vitro. The proliferation of HUVECs was evaluated by cell counting and CCK-8 assays, and migration was evaluated by the streaked plate assay. The expression levels of angiogenesis-associated genes and proteins in HUVECs were measured by qRT-PCR and Western blotting, respectively.
resultsDexamethasone in the OIM suppressed the proliferation and migration of HUVECs, inhibiting the formation of capillary-like structures. Our research showed that dexamethasone stimulated HUVECs to secrete tissue inhibitor of metalloproteinase (TIMP-3), which competed with vascular endothelial growth factor (VEGF-A) to bind to vascular endothelial growth factor receptor 2 (VEGFR2, KDR). This effect was related to inhibiting the phosphorylation of ERK and AKT, which are two downstream targets of KDR. However, under hypoxia, the enhanced expression of hypoxia-inducible factor-1α (HIF-1α) decreased the expression of TIMP-3 and promoted the phosphorylation of KDR, improving HUVEC angiogenesis in the coculture system.
conclusionCoculture of hypoxia-preconditioned HUVECs and MSCs showed robust angiogenesis and osteogenesis in OIM, which has important implications for prevascularization in bone tissue engineering in the future.
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