NF-κB plays a pivotal role in pathogenesis in general arthritis. However, the participation of NF-κB in inflammation of the temporomandibular joint (TMJ) is poorly understood. We examined NF-κB expression in rat TMJs with synovitis induced by condyle hypermobility. By immunohistochemistry, NF-κB immunoreactivity was found mainly in the cytoplasm, not the nucleus, of the synovial lining cells of induced-synovitis and control TMJs. Southwestern histochemistry, a new method for detecting transcription factors, showed greater NF-κB expression in the nucleus of the synovial lining cells in the hypertrophic synovium than in control synovium. Increased numbers of the synovial lining cells with immunoreactivity for inducible nitric oxide synthase (iNOS), which is transcriptionally regulated by NF-κB, were also seen in the inflamed synovium. These findings indicate that excess mechanical stress increases NF-κB activation in the TMJ and suggest that active NF-κB is involved in the progression of TMJ inflammation.

Synovial hyperplasia is a feature of degenerative temporomandibular joint (TMJ) disease. However, the mechanism by which hyperplasia progresses in the TMJ is unknown. Based on the hypothesis that the oxidative stress generated by mechanical loading causes degenerative changes in the TMJ synovium, we investigated the generation of the highly reactive species, peroxynitrite, and the occurrence of DNA damage in the synovium. After condylar hypermobility of rat TMJs, a marker of peroxynitrite, nitrotyrosine, was localized to the nuclei and cytoplasm of the synovial lining cells and fibroblasts in synovitis-induced TMJ. DNA single-strand breaks were found in the nuclei of the synovial cells only after enzyme treatment, whereas DNA double-strand breaks were not detected. These findings indicate that condylar hypermovement induces the proliferation of synovial cells, and suggest that oxidative stress leads to the progression of synovial hyperplasia via DNA damage of the synovial cells in TMJs after mechanical loading.

Nitric oxide (NO) is generated from Larginine by NO synthase (NOS) and has multiple functions under both physiological and pathological conditions. One isoform of NOS, inducible NOS (iNOS) is expressed in the cells such as macrophages after induction with various cytokines or mechanical stress. In this study, we investigated the distribution of iNOS, interleukin-1, (IL-1,) and its receptor, the IL-1 receptor (IL-1R), in the synovial membrane of the temporomandibular joint (TMJ) of normal rats using immunolight and immunoelectron microscopy. By light microscopy, an immunopositive reaction for iNOS and IL-1, was found in the superficial cells of the synovial membrane of both the anterior and posterior portions of the articular disc. Immunoelectron microscopy revealed that iNOSimmunoreactive products were deposited in the cytoplasm and vesicles, and on the plasma membrane of type-A (macrophage-like) and B (fibroblast-like) cells of the superficial layer. IL-1R-positive products were found both on the plasma membrane and in the vesicles of type-A cells of the synovial lining, and were observed in macrophages in the sublining layer. These results reveal that iNOS and IL-1, localize to the synovial membrane of the rat TMJ under physiological conditions. Therefore, it is likely that autocrine/paracrine effects of IL-1, induce NO generation by iNOS via the IL-1R in type-A cells. It is considered that cytokine-induced NO may play an important role in the physiological maintenance, e.g. self-protection, by synovial lining cells of the synovial membrane in the TMJ.