ArticleGene2007
EP4 receptor regulates collagen type-I, MMP-1, and MMP-3 gene expression in human tendon fibroblasts in response to IL-1 beta treatment.
Article in Gene, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.
What it found
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Who cites it
46 citing papers in PubMed, 105 citations in OpenAlex.
- Effect of platelet-rich plasma on the degenerative rotator cuff tendinopathy according to the compositions.Journal of orthopaedic surgery and research · 2019Trial
- Adjunctive use of combination of super-pulsed laser and light-emitting diodes phototherapy on nonspecific knee pain: double-blinded randomized placebo-controlled trial.Lasers in medical science · 2014Trial
- Prolyl-Hydroxyproline Promotes Structural Matrix Organization in 3D Equine Tendon Proper and Peritenon Post-Injury Model.Journal of orthopaedic research : official publication of the Orthopaedic Research Society · 2026Article
- Article
- Pathological Mechanisms of Tendinopathy Pain: From Mechanical Overload to Neuroimmune-Vascular Crosstalk.Pain research & management · 2026Review
- Current Mechanobiological Pathways and Therapies Driving Spinal Health.Bioengineering (Basel, Switzerland) · 2025Review
- Orthobiologics Revisited: A Concise Perspective on Regenerative Orthopedics.Current issues in molecular biology · 2025Review
- Comparison of bioactive substances in novel-developed freeze-dried platelet-rich plasma (PRP) and activated normal PRP, and investigation of bioactive substance levels after long-term storage.Regenerative therapy · 2024Article
- Recent developments in Achilles tendon risk-analyzing rupture factors for enhanced injury prevention and clinical guidance: Current implications of regenerative medicine.Journal of orthopaedic translation · 2024Review
- Sacral Bioneuromodulation: The Role of Bone Marrow Aspirate in Spinal Cord Injuries.Bioengineering (Basel, Switzerland) · 2024Review
- Is Curcumine Useful in the Treatment and Prevention of the Tendinopathy and Myotendinous Junction Injury? A Scoping Review.Nutrients · 2023Article
- Defining the Profile: Characterizing Cytokines in Tendon Injury to Improve Clinical Therapy.Journal of immunology and regenerative medicine · 2022Article
- Application of Orthobiologics in Achilles Tendinopathy: A Review.Life (Basel, Switzerland) · 2022Review
- Review
- The Effect of Age and Intrinsic Aerobic Exercise Capacity on the Expression of Inflammation and Remodeling Markers in Rat Achilles Tendons.International journal of molecular sciences · 2021Article
- [Clinical characteristics of crystal deposits in joints and tendons in patients with gout].Beijing da xue xue bao. Yi xue ban = Journal of Peking University. Health sciences · 2021Article
- Tendon healing is adversely affected by low-grade inflammation.Journal of orthopaedic surgery and research · 2021Review
- [Tendinopathies of the Achilles tendon].Zeitschrift fur Rheumatologie · 2021Article
- Effect of NIR Laser Therapy by MLS-MiS Source on Fibroblast Activation by Inflammatory Cytokines in Relation to Wound Healing.Biomedicines · 2021Article
- Bone Marrow Aspirate Matrix: A Convenient Ally in Regenerative Medicine.International journal of molecular sciences · 2021Review
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
Tendinopathy is accompanied by inflammation, tendon matrix degradation, or both. Inflammatory cytokine IL-1beta, which is a potent inflammatory mediator, is likely present within the tendon. The purpose of this study was to determine the biological impact of IL-1beta on tendon fibroblasts by assessing the expression of cPLA(2), COX-2, PGE(2) and its receptors (EPs), collagen type-I, and MMPs. We also studied the role of the p38 MAPK pathway in IL-1beta-induced catabolic effects. We found that IL-1beta increased the expression levels of cPLA(2) and COX-2, and also increased the secretion of PGE(2). Induction of MMPs, such as MMP-1 and MMP-3 at the mRNA level, was also observed after stimulation with IL-1beta. Furthermore, the presence of IL-1beta significantly decreased the level of collagen type-I mRNA in tendon fibroblasts. These effects were found to be mediated by selective upregulation of EP(4) receptor, which is a member of G-protein-coupled receptor that transduces the PGE(2) signal. Blocking EP(4) receptor by a specific chemical inhibitor abolished IL-1beta-induced catabolic effects. These results suggest that IL-1beta-induced catabolic action on tendon fibroblasts occurs via the upregulation of two key inflammatory mediators, cPLA(2) and COX-2, which are responsible for the synthesis of PGE(2). IL-1beta further stimulates the expression of EP(4) receptor, suggesting positive feedback regulation which may lead to accelerated catabolic processes in tendon fibroblasts. Studies using pathway-specific chemical inhibitors suggest that the p38 MAPK pathway is the key signaling cascade transducing IL-1beta-mediated catabolic effects. Collectively, our findings suggest that the EP(4) receptor mediates the IL-1beta-induced catabolic metabolism via the p38 MAPK pathway in human tendon fibroblasts and may play a major role in the tendon's degenerative changes often seen in the later stages of tendinopathy.
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What OpenQuestion holds
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.