ArticleArthritis research & therapy2009
Hypoxia upregulates angiogenesis and synovial cell migration in rheumatoid arthritis.
Article in Arthritis research & therapy, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers, 1 of them a synthesis that pooled it.
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Who cites it
43 citing papers in PubMed, 1 synthesis or guideline pooled it, 117 citations in OpenAlex.
- Current situation and trend of non-coding RNA in rheumatoid arthritis: a review and bibliometric analysis.Frontiers in immunology · 2023Pooled it
- Deviation from physiologically appropriate oxygen levels alters proliferation, cytokine production and proximal antigen receptor signalling in CD4+ memory T cells.Frontiers in immunology · 2026Article
- Targeting the synovial engine: next-generation engineered immune cells to eradicate pathogenic FLS in rheumatoid arthritis, with safety-first, selective designs.Frontiers in immunology · 2026Review
- Non-FDG PET/CT imaging of inflammatory arthritis.Skeletal radiology · 2025Review
- Endothelial cell-derived apoptotic bodies modulate innate and adaptive immune responses during inflammation.Cell communication and signaling : CCS · 2025Article
- Tetramethylpyrazine alleviates hypoxia-induced proliferation, migration, and inflammatory response of fibroblast-like synoviocytes via inhibiting the HIF-1α- circCDC42BPB pathway.Advances in rheumatology (London, England) · 2024Article
- New Potentiality of Bioactive Substances: Regulating the NLRP3 Inflammasome in Autoimmune Diseases.Nutrients · 2023Review
- HIF-1α dependent RhoA as a novel therapeutic target to regulate rheumatoid arthritis fibroblast-like synoviocytes migration in vitro and in vivo.Journal of orthopaedic translation · 2023Article
- DJ-1 controls T cell differentiation and osteoclastogenesis in rheumatoid arthritis.Scientific reports · 2022Article
- Cellular metabolic adaptations in rheumatoid arthritis and their therapeutic implications.Nature reviews. Rheumatology · 2022Review
- Matrix Metalloproteinases and Their Inhibitors in Pulmonary Fibrosis: EMMPRIN/CD147 Comes into Play.International journal of molecular sciences · 2022Review
- Elucidating the role of hypoxia-inducible factor in rheumatoid arthritis.Inflammopharmacology · 2022Review
- Association of serum hepatoma-derived growth factor levels with disease activity in rheumatoid arthritis: A pilot study.Journal of clinical laboratory analysis · 2022Article
- A narrative review of the role of the Notch signaling pathway in rheumatoid arthritis.Annals of translational medicine · 2022Review
- Analysis of Hepatic Lipid Metabolism and Immune Function During the Development of Collagen-Induced Arthritis.Frontiers in immunology · 2022Article
- Synovial Fibroblast Sialylation Regulates Cell Migration and Activation of Inflammatory Pathways in Arthritogenesis.Frontiers in immunology · 2022Article
- The role of renin angiotensin system in the pathophysiology of rheumatoid arthritis.Molecular biology reports · 2021Review
- Angiogenic cytokines can reflect the synovitis severity and treatment response to biologics in rheumatoid arthritis.Experimental & molecular medicine · 2020Article
- Targeting Opposing Immunological Roles of the Junctional Adhesion Molecule-A in Autoimmunity and Cancer.Frontiers in immunology · 2020Review
- Quantification of joint blood flow by dynamic contrast-enhanced near-infrared spectroscopy: application to monitoring disease activity in a rat model of rheumatoid arthritis.Journal of biomedical optics · 2020Article
Corrections and comments
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Authors and funding
6 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
introductionRheumatoid arthritis (RA) is characterised by invasion of cartilage, bone and tendon by inflamed synovium. Previous studies in our laboratory have shown that hypoxia is a feature of RA synovitis. In the present study, we investigated the consequences of hypoxia on angiogenesis and synovial fibroblast migration in RA.
methodsSynovial tissue was harvested from RA patients, and synovial membrane cells were cultured under conditions either of hypoxia (1% oxygen) or normoxia (21% oxygen). Protein levels of matrix metalloproteinases (MMPs) and angiogenic factors were measured, while RNA was extracted for PCR quantification of MMPs/tissue inhibitors of MMP (TIMPs) and angiogenic factors. Migration of RA synovial fibroblasts through collagen, and the effect of RA synovial cell supernatants in an in vitro angiogenesis assay, were utilised to determine the functional relevance of changes in mRNA/protein.
resultsWe observed upregulation under hypoxic conditions of MMPs responsible for collagen breakdown, specifically collagenase MMP-8, and the gelatinases MMP-2 and MMP-9, at both mRNA and protein levels. Increased MT1-MMP mRNA was also observed, but no effect on TIMP-1 or TIMP-2 was detected. RA fibroblast migration across collagen was significantly increased under hypoxic conditions, and was dependent on MMP activity. Furthermore, expression of angiogenic stimuli, such as vascular endothelial growth factor (VEGF), and VEGF/placental growth factor heterodimer, was also increased. Crucially, we show for the first time that hypoxia increased the angiogenic drive of RA cells, as demonstrated by enhanced blood vessel formation in an in vitro angiogenesis assay.
conclusionsHypoxia may be responsible for rendering RA synovial lining proangiogenic and proinvasive, thus leading to the debilitating features characteristic of RA.
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Registered trials
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.