ArticleScientific reports2017
Hypoxia regulates RhoA and Wnt/β-catenin signaling in a context-dependent way to control re-differentiation of chondrocytes.
Article in Scientific reports, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 25 citations in OpenAlex.
- Article
- History of hypoxia exposure aids future cell invasion according to cell type and collagen density.Molecular biology of the cell · 2025Article
- Hypoxia inducible factor 3-alpha promotes a malignant phenotype in colorectal cancer cells.IUBMB life · 2025Article
- Low-oxygen tension augments chondrocyte sensitivity to biomimetic thermomechanical cues in cartilage-engineered constructs.iScience · 2023Article
- Basic Properties of Adipose-Derived Mesenchymal Stem Cells of Rheumatoid Arthritis and Osteoarthritis Patients.Pharmaceutics · 2023Article
- RhoA Signaling in Neurodegenerative Diseases.Cells · 2022Review
- Cutting-Edge Technologies for Inflamed Joints on Chip: How Close Are We?Frontiers in immunology · 2022Review
- Strategies to Modulate the Redifferentiation of Chondrocytes.Frontiers in bioengineering and biotechnology · 2021Review
- Early Efficacy of Type I Collagen-Based Matrix-Assisted Autologous Chondrocyte Transplantation for the Treatment of Articular Cartilage Lesions.Frontiers in bioengineering and biotechnology · 2021Article
- Lipolysis by downregulating miR-92a activates the Wnt/β-catenin signaling pathway in hypoxic rats.Biomedical reports · 2020Article
- Phenotypic redifferentiation of dedifferentiated microtia chondrocytes through a three-dimensional chondrogenic culture system.American journal of translational research · 2020Article
- Regulation of RhoA GTPase and various transcription factors in the RhoA pathway.Journal of cellular physiology · 2018Review
- Articular Cartilage Aging-Potential Regenerative Capacities of Cell Manipulation and Stem Cell Therapy.International journal of molecular sciences · 2018Review
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Cartilage tissue is avascular and hypoxic which regulates chondrocyte phenotype via stabilization of HIFs. Here, we investigated the role of hypoxia and HIFs in regulation of Rho and canonical Wnt signaling in chondrocytes. Our data demonstrates that hypoxia controls the expression of RhoA in chondrocytes in a context-dependent manner on the culturing conditions. Within a 3D microenvironment, hypoxia suppresses RhoA on which hypoxia-driven expression of chondrogenic markers depends. Conversely, hypoxia leads to upregulation of RhoA in chondrocytes on 2D with a failure in re-expression of chondrogenic markers. Similarly to RhoA, hypoxic regulation of Wnt/β-catenin signaling depends on the microenvironment. Hypoxia downregulates β-catenin within 3D hydrogels whereas it causes a potent increase on 2D. Hypoxia-induced suppression of canonical Wnt signaling in 3D contributes to the promotion of chondrogenic phenotype as induction of Wnt signaling abrogates the hypoxic re-differentiation of chondrocytes. Inhibiting Wnt/β-catenin signaling via stabilization of Axin2 leads to a synergistic enhancement of hypoxia-induced expression of chondrogenic markers. The effects of hypoxia on Rho and Wnt/β-catenin signaling are HIF-dependent as stabilizing HIFs under normoxia revealed similar effects on chondrocytes. The study reveals important insights on hypoxic signaling of chondrocytes and how hypoxia regulates cellular mechanisms depending on the cellular microenvironment.
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