BackgroundPrimary frozen shoulder (FS) is a painful contracture of the glenohumeral joint that arises spontaneously without an obvious preceding event. Investigation of the intra-articular and periarticular pathology would contribute to the treatment of primary FS.Review of literatureMany studies indicate that the main pathology is an inflammatory contracture of the shoulder joint capsule. This is associated with an increased amount of collagen, fibrotic growth factors such as transforming growth factor-beta, and inflammatory cytokines such as tumor necrosis factor-alpha and interleukins. Immune system cells such as B-lymphocytes, T-lymphocytes and macrophages are also noted. Active fibroblastic proliferation similar to that of Dupuytren’s contracture is documented. Presence of inflammation in the FS synovium is supported by the synovial enhancement with dynamic magnetic resonance study in the clinical setting.ConclusionPrimary FS shows fibrosis of the joint capsule, associated with preceding synovitis. The initiator of synovitis, however, still remains unclear. Future studies should be directed to give light to the pathogenesis of inflammation to better treat or prevent primary FS.

Synovitis, which is characterized by the infiltration of inflammatory cells, often accompanies progression of temporomandibular joint disorder (TMD) symptoms. Because IL-1β is elevated in synovial fluids obtained from TMDs, we hypothesized that IL-1β-responsive genes in synoviocytes may help identify the putative genes associated with synovitis. Using microarray analysis, we found that monocyte chemoattractant protein-1 (MCP-1) mRNA levels were elevated in IL-1β-stimulated synoviocytes. MCP-1 is a member of the chemokine superfamily. The production of MCP-1 was increased in synoviocytes treated with IL-1β. When IL-1β was injected into the cavities of rat TMJs, inflammatory cells and MCP-1-positive cells were detected in the synovial tissues. Furthermore, MCP-1 levels were higher in synovial fluids from individuals with pain compared with those without pain. Inhibitors of MAP-kinases and NF-κB reduced IL-1β-induced MCP-1 production. These results suggest that MCP-1 stimulated by IL-1β is one of the factors associated with the inflammatory progression of TMDs.

BackgroundInterleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) are key mediators of the intracapsular pathological conditions of the temporomandibular joint (TMJ). Therefore, the gene expression profiles in synovial fibroblast-like cells (SFCs) from patients with internal derangement of the TMJ were examined after they were stimulated with IL-1β or TNF-α to determine which genes were altered.MethodsRibonucleic acid was isolated from SFCs after IL-1β or TNF-α treatment. Gene expression profiling was performed using oligonucleotide microarray analysis. On the basis of the results of this assay, we investigated the kinetics of macrophage inflammatory protein-3α (MIP-3α) gene expression using PCR, and protein production in TMJ SFCs stimulated by IL-1β or TNF-α using an ELISA. Inhibition experiments were performed with MAPK and NFκB inhibitors. SFCs were stimulated with IL-1β or TNF-α after treatment with inhibitors. The MIP-3α levels were measured using an ELISA.ResultsMacrophage inflammatory protein-3α was the gene most upregulated by IL-1β- or TNF-α stimulation. The mRNA and protein levels of MIP-3α increased in response to IL-1β in a time-dependent manner. In contrast, during TNF-α stimulation, the MIP-3α mRNA levels peaked at 4 h, and the protein levels peaked at 8 h. In addition, the IL-1β- and TNF-α-stimulated MIP-3α production was potently reduced by the MAPK and NFκB signaling pathway inhibitors.ConclusionInterleukin-1β and TNF-α increased the MIP-3α production in SFCs via the MAPK and NFκB pathways. These results suggest that the production of MIP-3α from stimulation with IL-1β or TNF-α is one factor associated with the inflammatory progression of the internal derangement of the TMJ.

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.

These data should provided useful information about the pathologic conditions of TMJ, especially in support of diagnosis and therapeutic approaches to TMJ.