Cyclic mechanical loading of human synovial cells in three-dimensional cultured tissue up-regulates gene expressions of inflammatory cytokines and matrix metalloproteinases

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Excessive mechanical stress is thought to be a factor in the development of temporomandibular joint disorders (TMJD) through the expression of matrix metalloproteinases (MMPs) and related cytokines. Previously we examined the effects of cyclic compressive loading on matrix degradation of three-dimensional (3D) tissues containing human synovium-derived cells for one hour per day for 5 or 15 consecutive days. However, it is still unknown how the expressions of MMPs and inflammatory cytokine genes change after cyclic compression for only one hour. To investigate the biological response of synovial joints to mechanical loading, we quantitatively analyzed the expression of these genes after cyclic compressive load on human synovial cells in three-dimensional cultured tissue for one hour. Human synovial cells were seeded onto a collagen scaffold and then 20kPa or 40kPa of cyclic compressive load was applied for one hour. mRNA levels for catabolic genes were examined immediately after and 6 hours after compressive loading. The mRNA expression levels of IL-1β, IL-6, IL-8, MMP-1, MMP-3 and MMP-9 were significantly increased 6 hours after cyclic compression. These findings provide new insights into the pathomechanism of TMJD via increased expression of MMPs and related cytokines by mechanical loading.