ArticleThe American journal of pathology2004
Mechanical overload induces VEGF in cartilage discs via hypoxia-inducible factor.
Article in The American journal of pathology, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers, 1 of them a synthesis that pooled it.
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Who cites it
53 citing papers in PubMed, 1 synthesis or guideline pooled it, 149 citations in OpenAlex.
- Biophysical Stimuli: A Review of Electrical and Mechanical Stimulation in Hyaline Cartilage.Cartilage · 2019Pooled it
- EYA1 promotes tumor angiogenesis in colorectal cancer by activating HIF-1β through LSD2-mediated H3K4me2 demethylation.Journal of cancer research and clinical oncology · 2025Article
- Article
- Mechanical Articular Cartilage Injury Models and Their Relevance in Advancing Therapeutic Strategies.Advances in experimental medicine and biology · 2023Article
- Understanding the Influence of Local Physical Stimuli on Chondrocyte Behavior.Advances in experimental medicine and biology · 2023Review
- Ciliary IFT88 Protects Coordinated Adolescent Growth Plate Ossification From Disruptive Physiological Mechanical Forces.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2022Article
- The essential anti-angiogenic strategies in cartilage engineering and osteoarthritic cartilage repair.Cellular and molecular life sciences : CMLS · 2022Review
- Heparan Sulfate Deficiency in Cartilage: Enhanced BMP-Sensitivity, Proteoglycan Production and an Anti-Apoptotic Expression Signature after Loading.International journal of molecular sciences · 2021Article
- Screening of key biomarkers of tendinopathy based on bioinformatics and machine learning algorithms.PloS one · 2021Article
- Intra-articular etanercept attenuates pain and hypoxia from TMJ loading in the rat.Journal of orthopaedic research : official publication of the Orthopaedic Research Society · 2020Article
- Intrabody against prolyl hydroxylase 2 promotes angiogenesis by stabilizing hypoxia-inducible factor-1α.Scientific reports · 2019Article
- Disordered Mechanical Stress and Tissue Engineering Therapies in Intervertebral Disc Degeneration.Polymers · 2019Review
- Erythropoietin inhalation enhances adult canine alveolar-capillary formation following pneumonectomy.American journal of physiology. Lung cellular and molecular physiology · 2019Article
- The Biomechanical Effect of the Sagittal Split Ramus Osteotomy on the Temporomandibular Joint: Current Perspectives on the Remodeling Spectrum.Frontiers in physiology · 2019Article
- Influence of disease-modifying antirheumatic drugs on oxidative and nitrosative stress in patients with rheumatoid arthritis.Inflammopharmacology · 2018Review
- Inflammatory Biomarker Profiling in Total Joint Arthroplasty and Its Relevance to Circulating Levels of Lubricin, a Novel Proteoglycan.Clinical and applied thrombosis/hemostasis : official journal of the International Academy of Clinical and Applied Thrombosis/Hemostasis · 2018Article
- The potential role of angiogenesis in the development of shoulder pain, shoulder dysfunction, and lymphedema after breast cancer treatment.Cancer management and research · 2018Review
- Vascular Endothelial Growth Factor in Cartilage Development and Osteoarthritis.Scientific reports · 2017Article
- Pharmacological treatment with diacerein combined with mechanical stimulation affects the expression of growth factors in human chondrocytes.Biochemistry and biophysics reports · 2017Article
- Chondrogenic progenitor cells promote vascular endothelial growth factor expression through stromal-derived factor-1.Osteoarthritis and cartilage · 2017Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
VEGF (vascular endothelial growth factor) is not only one of the most important angiogenesis factors, but is involved also in inflammatory processes. Recent studies have shown that VEGF as well as its receptor VEGFR-2 are expressed on osteoarthritic chondrocytes, but not on normal adult chondrocytes. Since mechanical overload is one of the causative factors for osteoarthritis, we studied its effect on VEGF expression on bovine cartilage disks that were compressed once with a strain of 50% and a strain rate of 1/second. Under these conditions, control disks (without pressure) were completely negative for VEGF expression as evidenced by immunocytochemical stainings as well as by enzyme-linked immunosorbent assay (ELISA) measurements. In contrast, 4 days after mechanical overload, the cartilage disks were positive in both detection methods. In addition, after mechanical overload chondrocytes were strongly immunopositive for hypoxia-inducible factor-1alpha (HIF-1alpha), the limiting protein of the dimeric transcription factor HIF-1 that is known to induce VEGF expression. Furthermore, the matrix metalloproteases MMP-1, MMP-3, and MMP-13, could be easily detected in pressure-treated disks by immunohistochemistry whereas staining in controls was low or undetectable. The tissue inhibitors of metalloproteinases (TIMP-1 and -2) could be detected in controls but not in samples treated with mechanical overload. To prove that increased MMP or decreased TIMP expression could be a result of the autocrine action of VEGF on chondrocytes, we repeated the experiments in the presence of a specific inhibitor for the kinase activity of the VEGFR-2. This inhibitor was effective to reduce mechanically induced MMP-1, -3, and -13 immunostaining and to restore TIMP expression. Taking together, these findings indicate that VEGF is induced in chondrocytes by mechanical overload and mediates destructive processes in osteoarthritis as an autocrine factor.
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