ArticleJournal of orthopaedic surgery and research2016
Activation of calcitonin gene-related peptide signaling through the prostaglandin E2-EP1/EP2/EP4 receptor pathway in synovium of knee osteoarthritis patients.
Article in Journal of orthopaedic surgery and research, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 33 citations in OpenAlex.
- Persistent prostaglandin E2 upregulation and hormonal multi-resistance: A hypothesis for long COVID.Biochemistry and biophysics reports · 2026Article
- STING mediates experimental osteoarthritis and mechanical allodynia in mouse.Arthritis research & therapy · 2023Article
- Potential Anti-Inflammatory and Chondroprotective Effect ofInternational journal of molecular sciences · 2022Article
- Experimental models to study osteoarthritis pain and develop therapeutics.Osteoarthritis and cartilage open · 2022Review
- Involvement of the calcitonin gene-related peptide system in the modulation of inflamed uterus contractile function in pigs.Scientific reports · 2022Article
- A High Body Mass Index and the Vacuum Phenomenon Upregulate Pain-Related Molecules in Human Degenerated Intervertebral Discs.International journal of molecular sciences · 2022Article
- Article
- CGRP Regulates Nucleus Pulposus Cell Apoptosis and Inflammation via the MAPK/NF-Oxidative medicine and cellular longevity · 2021Article
- Serum Calcitonin Gene-Related Peptide and Receptor Protein Levels in Patients With Fibromyalgia Syndrome: A Cross-Sectional Study.Archives of rheumatology · 2020Article
- Transforming growth factor-β stimulates nerve growth factor production in osteoarthritic synovium.BMC musculoskeletal disorders · 2019Article
- Inflammation-linked adaptations in dermal microvascular reactivity accompany the development of obesity and type 2 diabetes.International journal of obesity (2005) · 2019Article
- Osteoarthritis patients with high haemoglobin A1c have increased Toll-like receptor 4 and matrix metalloprotease-13 expression in the synovium.Diabetes, metabolic syndrome and obesity : targets and therapy · 2019Article
- Contribution of Infrapatellar Fat Pad and Synovial Membrane to Knee Osteoarthritis Pain.BioMed research international · 2019Review
- Increase in mast cell marker expression in the synovium of obese patients with osteoarthritis of the knee.Diabetes, metabolic syndrome and obesity : targets and therapy · 2019Article
- Article
- Regulation of calcitonin gene-related peptide expression through the COX-2/mPGES-1/PGE2 pathway in the infrapatellar fat pad in knee osteoarthritis.Lipids in health and disease · 2018Article
- Vascular endothelial growth factor expression and their action in the synovial membranes of patients with painful knee osteoarthritis.BMC musculoskeletal disorders · 2018Article
- Down-regulation of microsomal prostaglandin E2 synthase-1 in the infrapatellar fat pad of osteoarthritis patients with hypercholesterolemia.Lipids in health and disease · 2018Article
- Transforming growth factor activating kinase 1 regulates extracellular matrix degrading enzymes and pain-related molecule expression following tumor necrosis factor-α stimulation of synovial cells: an in vitro study.BMC musculoskeletal disorders · 2017Article
- Expression of calcitonin gene-related peptide in the infrapatellar fat pad in knee osteoarthritis patients.Journal of orthopaedic surgery and research · 2017Article
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Authors and funding
11 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundCalcitonin gene-related peptide (CGRP) is a 37-amino-acid vasodilatory neuropeptide that binds to receptor activity-modifying protein 1 (RAMP1) and the calcitonin receptor-like receptor (CLR). Clinical and preclinical evidence suggests that CGRP is associated with hip and knee joint pain; however, the regulation mechanisms of CGRP/CGRP receptor signaling in synovial tissue are not fully understood.
methodsSynovial tissues were harvested from 43 participants with radiographic knee osteoarthritis (OA; unilateral Kellgren/Lawrence (K/L) grades 3-4) during total knee arthroplasty. Correlationships between the mRNA expression levels of CGRP and those of tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, IL-6, and cycloxygenase-2 (COX-2) were evaluated using real-time PCR analysis of total RNA extracted from the collected synovial tissues. To investigate the factors controlling the regulation of CGRP and CGRP receptor expression, cultured synovial cells were stimulated with TNF-α, IL-1β, IL-6, and prostaglandin E2 (PGE2) and were also treated with PGE2 receptor (EP) agonist.
resultsCGRP and COX-2 localized in the synovial lining layer. Expression of COX-2 positively correlated with CGRP mRNA expression in the synovial tissue of OA patients. The gene expression of CGRP and RAMP1 increased significantly in synovial cells exogenously treated with PGE2 compared to untreated control cells. In cultured synovial cells, CGRP gene expression increased significantly following EP4 agonist treatment, whereas RAMP1 gene expression increased significantly in the presence of exogenously added EP1 and EP2 agonists.
conclusionsPGE2 appears to regulate CGRP/CGRP receptor signaling through the EP receptor in the synovium of knee OA patients.
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