ArticleStem cell research & therapy2015
HIF-1A and C/EBPs transcriptionally regulate adipogenic differentiation of bone marrow-derived MSCs in hypoxia.
Article in Stem cell research & therapy, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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Who cites it
39 citing papers in PubMed, 67 citations in OpenAlex.
- C/EBPδ as a Regulatory Node in Adipocytes: Roles in Differentiation, Metabolism, and Immune Function.Biomolecules · 2026Review
- CircVPS13C Promotes Intramuscular Adipogenesis via MiR-5606-X-Biomolecules · 2026Article
- Insights Into the HIF-1α-Mediated NLRP3 Pyroptosis Pathway in the Regulation of Musculoskeletal Diseases in the High-Altitude Environment.Journal of inflammation research · 2026Review
- miR-365 promotes HOXA9-mediated differentiation of mesenchymal stem cells to nucleus pulposus cells by interacting with HIF-1α.World journal of orthopedics · 2025Article
- Basic biology and roles of CEBPD in cardiovascular disease.Cell death discovery · 2025Review
- Hypoxia Promotes the Stemness of Mesangiogenic Progenitor Cells and Prevents Osteogenic but not Angiogenic Differentiation.Stem cell reviews and reports · 2024Article
- Induction of lncRNA MALAT1 by hypoxia promotes bone formation by regulating the miR-22-3p/CEBPD axis.Histology and histopathology · 2023Article
- The Role of HIF-1α in Bone Regeneration: A New Direction and Challenge in Bone Tissue Engineering.International journal of molecular sciences · 2023Review
- CEBPD is a master transcriptional factor for hypoxia regulated proteins in glioblastoma and augments hypoxia induced invasion through extracellular matrix-integrin mediated EGFR/PI3K pathway.Cell death & disease · 2023Article
- Review
- Mesenchymal/stromal stem cells: necessary factors in tumour progression.Cell death discovery · 2022Review
- Heterogeneity of tumor microenvironment is associated with clinical prognosis of non-clear cell renal cell carcinoma: a single-cell genomics study.Cell death & disease · 2022Article
- Hypoxia Modulates Regenerative Potential of Fetal Stem Cells.Applied sciences (Basel, Switzerland) · 2022Article
- Exosomes from cisplatin-induced dormant cancer cells facilitate the formation of premetastatic niche in bone marrow through activating glycolysis of BMSCs.Frontiers in oncology · 2022Article
- Hypoxia Inhibits Osteogenesis and Promotes Adipogenesis of Fibroblast-like Synoviocytes via Upregulation of Leptin in Patients with Rheumatoid Arthritis.Journal of immunology research · 2022Article
- Strategies to improve regenerative potential of mesenchymal stem cells.World journal of stem cells · 2021Review
- Review
- Article
- To Breathe or Not to Breathe: The Role of Oxygen in Bone Marrow-Derived Mesenchymal Stromal Cell Senescence.Stem cells international · 2021Review
- Hypoxic bone marrow mesenchymal cell-extracellular vesicles containing miR-328-3p promote lung cancer progression via the NF2-mediated Hippo axis.Journal of cellular and molecular medicine · 2021Article
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
introductionBone marrow-derived mesenchymal stem cells (BMSCs, also known as bone marrow-derived mesenchymal stromal cells) are known to be a component of the tumor microenvironment. BMSCs are multipotent stromal cells that can differentiate into a variety of cell types, including osteocytes, chondrocytes, adipocytes, epithelial cells and endothelial cells. Stem cells found in niches or transplanted into injured tissues constantly encounter hypoxic stress. Areas with very low to no oxygen pressure exist in solid tumors. The differentiation capacity of BMSCs under hypoxic conditions remains controversial.
methodsIn this study, a hypoxic workstation, set at an oxygen concentration of 0.2% was used to mimic the hypoxic microenvironment of cancer in vivo. Oil red O staining and alkaline phosphatase staining were used to examine the adipogenic or osteogenic differentiation, respectively, of BMSCs. Real-time PCR was performed to explore the expression of adipocyte- or osteocyte-specific genes. An RT2 Profiler™ PCR Array was used to screen a panel of 84 genes associated with human adipogenesis in BMSCs under normal and hypoxic conditions. A dual-luciferase reporter assay and chromatin immunoprecipitation (ChIP) were applied to analyze promoter activity to evaluate the possible regulatory mechanism of adipocyte-specific gene expression.
resultsWe found that this extreme hypoxia impaired osteogenic differentiation as indicated by the attenuation of alkaline phosphatase (ALP) activity and the reduced expression of osteogenic markers osteocalcin and osteopontin. Moreover, extreme hypoxia enhanced adipogenic differentiation, as indicated by the accumulation of lipid droplets and the expression of the adipocyte-specific genes leptin, LPL, CFD, PGAR and HIG2. In the extreme hypoxic conditions (0.2% oxygen), the overexpression of CCAAT enhancer-binding proteins (C/EBPs), especially C/EBPδ, and HIF-1A upregulated the promoter activities of adipocyte-specific genes such as leptin, CFD, HIG2, LPL, PGAR. In the present study, peroxisome proliferator-activated receptor-gamma (PPARγ) exerted a negative effect on the differentiation of BMSCs into adipocytes.
conclusionsIn view of these findings, extreme hypoxia induced the adipogenic differentiation of BMSCs through HIF-1A and C/EBPs. These findings might provide clues regarding the roles of BMSCs in the cancer microenvironment.
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