Gene Expression Profiling of IL-17A-Treated Synovial Fibroblasts from the Human Temporomandibular Joint.

Synovial fibroblasts contribute to the inflammatory temporomandibular joint under pathogenic stimuli. Synovial fibroblasts and T cells participate in the perpetuation of joint inflammation in a mutual activation feedback, via secretion of cytokines and chemokines that stimulate each other. IL-17 is an inflammatory cytokine produced primarily by Th17 cells which plays critical role in the pathogenesis of numerous autoimmune and inflammatory diseases. Here, we investigated the roles of IL-17A in temporomandibular joint disorders (TMD) using genome-wide analysis of synovial fibroblasts isolated from patients with TMD. IL-17 receptors were expressed in synovial fibroblasts as assessed using real-time PCR. Microarray analysis indicated that IL-17A treatment of synovial fibroblasts upregulated the expression of IL-6 and chemokines. Real-time PCR analysis showed that the gene expression of IL-6, CXCL1, IL-8, and CCL20 was significantly higher in IL-17A-treated synovial fibroblasts compared to nontreated controls. IL-6 protein production was increased by IL-17A in a time- and a dose-dependent manner. Additionally, IL-17A simulated IL-6 protein production in synovial fibroblasts samples isolated from three patients. Furthermore, signal inhibitor experiments indicated that IL-17-mediated induction of IL-6 was transduced via activation of NFκB and phosphatidylinositol 3-kinase/Akt. These results suggest that IL-17A is associated with the inflammatory progression of TMD.

Primary frozen shoulder: brief review of pathology and imaging abnormalities.

BACKGROUND: Primary 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 LITERATURE: Many 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. CONCLUSION: Primary 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.

Pulmonary embolism after arthroscopic rotator cuff repair: a case report.

Total hip/knee arthroplasty may cause venous thromboembolism (VTE) as a postoperative complication. However, there are few reports on VTE after arthroscopic shoulder surgery. We report a patient who developed pulmonary embolism (PE) 6 days after arthroscopic rotator cuff repair but recovered without sequelae. In this case, the possibility of DVT of the lower limbs was denied by contrast-enhanced CT. Most possibly, the source of PE was deep vein thrombosis (DVT) of the upper limb under Desault fixation which showed arthroscopic surgery-related swelling postoperatively.

Effects of interleukin-1ß and tumor necrosis factor-α on macrophage inflammatory protein-3α production in synovial fibroblast-like cells from human temporomandibular joints.

BACKGROUND: Interleukin-1ß (IL-1ß) 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-1ß or TNF-α to determine which genes were altered. METHODS: Ribonucleic acid was isolated from SFCs after IL-1ß 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-1ß or TNF-α using an ELISA. Inhibition experiments were performed with MAPK and NFκB inhibitors. SFCs were stimulated with IL-1ß or TNF-α after treatment with inhibitors. The MIP-3α levels were measured using an ELISA. RESULTS: Macrophage inflammatory protein-3α was the gene most upregulated by IL-1ß- or TNF-α stimulation. The mRNA and protein levels of MIP-3α increased in response to IL-1ß 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-1ß- and TNF-α-stimulated MIP-3α production was potently reduced by the MAPK and NFκB signaling pathway inhibitors. CONCLUSION: Interleukin-1ß 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-1ß or TNF-α is one factor associated with the inflammatory progression of the internal derangement of the TMJ.

The anti-inflammatory effect of cyclooxygenase inhibitors in fibroblast-like synoviocytes from the human temporomandibular joint results from the suppression of PGE2 production.

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-1ß-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-1ß. 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.

Microarray analysis of IL-1beta-stimulated chemokine genes in synovial fibroblasts from human TMJ.

BACKGROUND: Interleukin (IL)-1beta is thought to play a key role in several pathologic conditions of the temporomandibular joint (TMJ). Gene expression profile of synovial fibroblasts stimulated with IL-1beta was studied by oligonucleotide microarray analysis to elucidate candidate genes associated with intracapsular pathologic conditions of TMJ. METHODS: RNA was isolated from synovial fibroblasts from five patients after IL-1beta treatment. Gene expression profiling was performed with a GeneChip. Changes in gene expression were determined by comparing IL-1beta-treated cells with untreated cells. RESULTS: A total of 121 genes showed a greater than threefold difference in average intensity between untreated and IL-1beta-treated synovial fibroblasts in five experiments. Five chemokines were among the 10 most upregulated genes, and the most upregulated gene was CCL20. The 121 IL-1beta-responsive genes included 12 chemokines whose mRNA levels were confirmed by real-time PCR. CONCLUSION: These data should provided useful information about the pathologic conditions of TMJ, especially in support of diagnosis and therapeutic approaches to TMJ.