The expression of COX-2, but not the expression of COX-1, was found to be elevated in a disease-related pattern in the synovial tissue from patients with RA, AS, or PsA in comparison with OA samples, and was especially high in AS synovial tissue.
To evaluate the in vitro effects of diacerhein, a new drug for the treatment of osteoarthritis (OA), and its active metabolite, rhein, on the production of nitric oxide (NO), prostaglandin (PGE2), cyclooxygenase-2 (COX-2), as well as the production and expression of the inducible nitric oxide synthase (iNOS) in human OA chondrocytes.
PPAR-mediated induction of COX-2 expression and synthesis in human OA synovial fibroblasts is inhibited by therapeutic concentrations of NIM through the functional antagonism of ligand-dependent receptor activation, with the resultant suppression of PPAR-dependent transactivation of target genes (e.g., COX-2).
In the present study, we report the pharmacological effects of green tea polyphenol epigallocatechin-3-gallate (EGCG), on interleukin-1 beta (IL-1 beta)-induced expression and activity of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) in human chondrocytes derived from osteoarthritis (OA) cartilage.
Celecoxib, the first US FDA approved selective COX-2 inhibitor, initially developed for the treatment of adult rheumatoid arthritis and osteoarthritis, has been reported to reduce the formation of polyps in patients with familial adenomatous polyposis.
Here, we determined that the elevated PGE2 levels in the high OA subgroup were linked with enhanced cyclooxygenase-2 (COX-2) protein levels compared to normal and low OA Ob.
Long term NSAID treatment inhibits COX-2 synthesis in the knee synovial membrane of patients with osteoarthritis: differential proinflammatory cytokine profile between celecoxib and aceclofenac.
Our results and previous studies on the role of the cyclooxygenase 2 enzyme encoded by PTGS2 underscore the importance of this signaling pathway in the pathogenesis of knee OA.
GWAS have reported structural genes (COL6A4), inflammation-related genes (PTGS2/PLA2G4A) and a locus on chr 7q22 (GPR22 and four other genes in the same linkage disequilibrium block) associated with osteoarthritis.
Contribution of H3K4 methylation by SET-1A to interleukin-1-induced cyclooxygenase 2 and inducible nitric oxide synthase expression in human osteoarthritis chondrocytes.
The authors performed further measurements of MMP-13 production in osteoarthritis chondrocytes stimulated by the EP2 agonist butaprost in the presence or absence of interleukin-1β (IL-1β) and/or cyclooxygenase-2 (COX-2) inhibitor.
Interleukin-1β (IL-1β) markedly up-regulated ERRα expression in OA chondrocytes in vitro, and agonist or inhibitor treatment indicated that the up-regulation was dependent on cyclooxygenase 2 (COX-2; NS398), prostaglandin E(2), cAMP (8-bromo-cAMP), and protein kinase A (PKA; KT5720).
Conventional medical treatment for rheumatoid arthritis and osteoarthritis includes the use of NSAIDs (traditional and selective inhibitors of cyclooxygenase [COX]-2), because they provide unmistakable and significant health benefits in the treatment of pain and inflammation.
As interleukin-1β (IL-1β) is one of the key proinflammatory cytokines contributing to the progression in osteoarthritis, we investigated the effect of celastrol, a triterpenoid compound extracted from the Chinese herb Tript erygium wilfordii Hook F, in neutralizing the inflammatory effects of IL-1β on MMPs, iNOS and COX-2 expression as well as nitric oxide (NO) and prostaglandin E2 (PGE2) production.
Cyclooxygenase-2 (COX-2) is a major prostaglandin E2 (PGE2) synthetic enzyme and is involved in the pathogenesis of chronic inflammation and pain in osteoarthritis (OA).
Using rabbit and human synovial fibroblast cell lines, we examined the effects of Cx43 overexpression and Cx43 siRNA-mediated knockdown on the gene expression of OA-associated matrix metalloproteinases (MMP1 and MMP13), aggrecanases (ADAMTS4 and ADAMTS5), and inflammatory factors (IL1, IL6 and PTGS2) by quantitative real time RT-PCR.
EGCG treatment consistently up-regulated the IL-1β-decreased hsa-miR-199a-3p expression (P < 0.05) and significantly inhibited the IL-1β-induced COX-2 expression/PGE<sub>2</sub> production (P < 0.05) in OA chondrocytes transfected with anti-hsa-miR-199a-3p.
This study elucidates the detailed mechanism of low shear stress regulating the resistin-induced catabolic COX-2 expression and indicates a possible reparative role of moderate shear force in resistin-stimulated OA development..