Abstract
Background Non-steroidal anti-inflammatory drugs (NSAIDs) have been widely used for the management of pain and inflammation. However, little remains known about the effects of NSAIDs on synovitis of the human temporomandibular joint (TMJ). The aims of this study were to investigate the potential anti-inflammatory effects of NSAIDs on synovitis of the TMJ and the inflammatory effects of PGE2 on fibroblast-like synoviocytes (FLS) derived from the TMJ.Methods Human synovial tissue was obtained from patients with internal derangement who underwent arthroscopy of the TMJ. FLSs were prepared from the tissues using the outgrowth method. A COX inhibitor (indomethacin or celecoxib) was added to the IL-1β-stimulated cells in culture. The cells were also stimulated with PGE2 or an EP agonist. The PGE2 production and COX-2 and IL-6 expression levels were examined using enzyme-linked immunosorbent assays, real-time PCR, and a microarray analysis.Results COX inhibitors decreased not only PGE2 production, but also the expression of COX-2 and IL-6 in FLS stimulated with IL-1β. EP2 and EP4 were both expressed in the FLS, and the treatment with EP2 and EP4 agonists induced IL-6 production in these cells.Conclusion The COX inhibitors indomethacin and celecoxib reduce the expression of inflammatory factors, such as COX-2 and IL-6, in FLS from the TMJ via suppression of PGE2 production. EP2 and EP4 were the main receptors for PGE2 present in the FLS. The approach used in this study may be useful for revealing how drugs such as NSAIDs affect the cellular functions of FLS from the TMJ.
Highlights
Synovitis, which often accompanies intracapsular pathological conditions, such as disk displacement (DD)/internal derangement (ID) and osteoarthritis (OA) of the temporomandibular joint (TMJ), is characterized by chronic inflammatory changes [1, 2]
Effects of COX inhibitors on PGE2 generation To examine the effect of COX inhibitors on PGE2 generation, fibroblast-like synoviocytes (FLS) were treated with 1 lM or 10 lM indomethacin or 1 lM or 10 lM celecoxib after being stimulated with IL-1b
Effect of COX inhibitors on IL-6 expression To examine the anti-inflammatory effect of COX inhibitors, the gene expression and protein production of IL-6 were measured in IL-1b-stimulated FLS treated with or without COX inhibitors
Summary
Synovitis, which often accompanies intracapsular pathological conditions, such as disk displacement (DD)/internal derangement (ID) and osteoarthritis (OA) of the temporomandibular joint (TMJ), is characterized by chronic inflammatory changes [1, 2]. In a previous study performed to identify the putative genes associated with inflammation in synovitis of the TMJ, we used a microarray analysis to investigate the IL-1b-responsive genes in fibroblast-like synoviocytes (FLS) derived from patients with ID or OA [10]. PGE2 has been shown to modulate bone resorption by stimulating osteoclast formation from precursor stem cells [15, 16]. All of these results suggest that PGE2 is implicated in the inflammation and tissue destruction that characterize arthritic diseases. CONCLUSION: The COX inhibitors indomethacin and celecoxib reduce the expression of inflammatory factors, such as COX-2 and IL-6, in FLS from the TMJ via suppression of PGE2 production.
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