Celecoxib down-regulates mechanically induced ADAMTS-4 gene expression in 3D cultured tissue of human synovium-derived cells at lower concentration than indomethacin

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Cyclic mechanical load is thought to play a major role in temporomandibular disorder (TMD). We developed the cyclic loading bioreactor, in which matrix metalloproteases (MMPs) and a disintegrin, and metalloproteinase with thrombospondin motifs (ADAMTSs) are induced by mechanical stimulation to three-dimensional (3D) cultured tissue. The purpose of this study was to examine the effects of NSAIDs on the gene expressions of ADAMTSs, MMPs, and the protein expression of PGE2. Human synovial cells were seeded onto a collagen scaffold to construct 3D cultured tissue. Celecoxib or indomethacin were added to the culture media before cyclic compressive load. Cyclic compression was then applied to 3D tissues. After 6 hours, the media were assayed for PGE2 by HTRF^[○!R]. The mRNA expression of the 3D tissue was quantitatively determined by real time RT-PCR. We found that mechanical stress to the human synovial cells in 3D culture induced PGE2 production and up-regulated ADAMTS-4 and MMP-1, -3 gene expression. Celecoxib and indomethacin suppressed PGE2. Celecoxib down-regulated mechanically induced ADAMTS-4 gene expression at a lower concentration than indomethacin. These results indicate that celecoxib and indomethacin may have an inhibitory effect on cartilage destruction caused by mechanical stimulus. In addition, celecoxib may contribute to inhibition of cartilage destruction at a lower concentration than indomethacin.