Analysis of the stress signaling pathway using synovial cells from human temporomandibular joint and application to a gene therapy.

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Mechanical stress is thought to play a crucial role in the regulation of bone metabolism. Excessive mechanical loading has been reported to damage articular tissues directly or indirectly, and it is considered to be one of the factors affecting to onset and progression of temporomandibular joint disorders (TMDs). However, the exact pathophysiology of TMD has not been elucidated. In this study, we particularly focused on synovial cells and attempted to reveal the mechanism of joint destruction and repair by synovial cells loaded excessive mechanical stress. We have established a synovial lining cell strain, designated SGA2 cells, from human TMJ. SGA2 cells expressed the fibroblastic markers vimentin and prolyl 4-hydroxylase ; they also expressed laminin and heat shock protein 27, all of which are markers of type B cells. These results suggested that SGA2 cells derived from synovial lining type B cells. However, some cells expressed the macrophage marker CD 68, suggesting that they were derived from intermediate type synovial lining cells, expressing both type A and type B cell markers. Mechanical stretch enhanced the expression of RANKL, MMPs (MMP-3, MMP-13) and inflammatory mediators (IL-1beta, TNF-alpha, iNOS) in synovial cells. These results suggested that synovial cells loaded excessive mechanical stress promoted osteoclast differentiation, degraded bone matrix and produced several inflammatory mediators. Under appropriate culture conditions, SGA2 cells differentiated into the osteoblast, chondrocyte and adipocyte. These results suggested that the synovial membrane of adult human temporomandibular joint contains MSCs with the capacity to differentiate along osteogenic, chondrogenic or adipogenic lineages, and that this synovial membrane-derived MSCs are likely to contribute to joint regeneration in arthritis.