ArticleMediators of inflammation2013
Thrombin promotes matrix metalloproteinase-13 expression through the PKCδ c-Src/EGFR/PI3K/Akt/AP-1 signaling pathway in human chondrocytes.
Article in Mediators of inflammation, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 42 citations in OpenAlex.
- Cartilage degeneration is associated with activation of the PI3K/AKT signaling pathway in a growing rat experimental model of developmental trochlear dysplasia.Journal of advanced research · 2022Trial
- Exploring the mechanisms of arthritic diseases induced by aflatoxin B1 through comprehensive network analysis.International journal of surgery (London, England) · 2026Article
- Epidermal growth factor receptor signaling modulates postoperative pain and inflammatory responses.Frontiers in immunology · 2026Review
- Mulberroside A alleviates osteoarthritis via restoring impaired autophagy and suppressing MAPK/NF-κB/PI3K-AKT-mTOR signaling pathways.iScience · 2023Article
- Targeting transcription factors for therapeutic benefit in rheumatoid arthritis.Frontiers in immunology · 2023Review
- Estrogen alleviates post-traumatic osteoarthritis progression and decreases p-EGFR levels in female mouse cartilage.BMC musculoskeletal disorders · 2022Article
- The probable role and therapeutic potential of the PI3K/AKT signaling pathway in SARS-CoV-2 induced coagulopathy.Cellular & molecular biology letters · 2022Review
- Genome-wide DNA methylation study identifies significant epigenomic changes associated with internalized stigma in adults with non-specific chronic low back pain.Frontiers in pain research (Lausanne, Switzerland) · 2022Article
- Article
- Protease Activated Receptors and Arthritis.International journal of molecular sciences · 2021Review
- Network analysis indicating the pharmacological mechanism of Yunpi-Qufeng-Chushi-prescription in prophylactic treatment of rheumatoid arthritis.BMC complementary medicine and therapies · 2021Article
- AMPK Signaling in Energy Control, Cartilage Biology, and Osteoarthritis.Frontiers in cell and developmental biology · 2021Review
- Review
- Pathogenesis of Osteoarthritis: Risk Factors, Regulatory Pathways in Chondrocytes, and Experimental Models.Biology · 2020Review
- Activation of Protein Kinase Cδ Contributes to the Induction of Src/EGF Receptor/ERK Signaling in Ammonia-treated Astrocytes.Journal of molecular neuroscience : MN · 2020Article
- Putative functional variants of PI3K/AKT/mTOR pathway are associated with knee osteoarthritis susceptibility.Journal of clinical laboratory analysis · 2020Article
- Systems biology reveals how altered TGFβ signalling with age reduces protection against pro-inflammatory stimuli.PLoS computational biology · 2019Article
- Protease-activated receptors (PARs): mechanisms of action and potential therapeutic modulators in PAR-driven inflammatory diseases.Thrombosis journal · 2019Review
- Visfatin Promotes IL-6 and TNF-α Production in Human Synovial Fibroblasts by Repressing miR-199a-5p through ERK, p38 and JNK Signaling Pathways.International journal of molecular sciences · 2018Article
- EGFR is a pivotal regulator of thrombin-mediated inflammation in primary human nucleus pulposus culture.Scientific reports · 2017Article
Corrections and comments
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Authors and funding
6 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Thrombin is a key mediator of fibrin deposition, angiogenesis, and proinflammatory processes. Abnormalities in these processes are primary features of rheumatoid arthritis and osteoarthritis. Matrix metalloproteinase-13 (MMP-13) may contribute to the breakdown of articular cartilage during arthritis. However, the role of thrombin in MMP-13 production in chondrocytes is unknown. In this study, we investigated the intracellular signaling pathways involved in thrombin-induced MMP-13 expression in human chondrocytes. We found that stimulation with thrombin led to increased secretion of MMP-13 in cultured human chondrocytes. Further, this thrombin-induced MMP-13 production was reduced after transfection with siRNAs against protease activated receptors 1 and 3 (PAR1 and PAR3), but not with PAR4 siRNA. Treatment with specific inhibitors for PKCδ, c-Src, EGFR, PI3K, Akt, or AP-1 or with the corresponding siRNAs against these signaling proteins also abolished the thrombin-mediated increase in MMP-13 production in chondrocytes. Our results provide evidence that thrombin acts through the PAR1/PAR3 receptors and activates PKCδ and c-Src, resulting in EGFR transactivation and activation of PI3K, Akt, and finally AP-1 on the MMP-13 promoter, thereby contributing to cartilage destruction during arthritis.
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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.