Celecoxib down-regulates mechanically induced ADAMTS-4 gene expression in 3D cultured tissue of human synovium-derived cells at lower concentration than indomethacin
Temporomandibular disorder (TMD) is a disease or disorder of the temporomandibular joint and maticatory muscles that is sometimes caused by anterior displacement of the articular discs. When clenching the teeth, compressive force is applied directly to the synovium in the disc, which is displaced anteriorly, causing synovitis. Increased levels of inflammatory modulators, such as cytokines, nitric oxide, and cartilage matrix catabolites, as well as matrix metalloproteinases (MMPs), are found in the synovial fluid with TMD. MMPs derived from fibrocartilage and cartilage cells are considered key enzymes that are responsible for extracellular matrix (ECM) breakdown in the TMJ. Further, in recent years, not only MMPs, but also a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS) have been attracting attention as proteinases that degrade the ECM of cartilage. Among them, especially ADAMTS-4 and ADAMTS-5 are known to degrade aggrecan in the extracellular matrix. 7 Until now, an arthritis model was produced by stimulation of IL-1β, tension stress, and hydrostatic fluid pressure. We have developed a novel arthritis model using a cyclic loading bioreactor (CLS-7J ; Technoview, Osaka, Japan), and cultured human synovial cells in a three-dimensional (3D) cell-scaffold Celecoxib down-regulates mechanically induced ADAMTS-4 gene expression in 3D cultured tissue of human synovium-derived cells at lower concentration than indomethacin