Cyclic compressive mechanical loading on three­dimensional cultured tissue of human chondrocytes synergistically upregulates MMP­-3 gene expression with IL­-1β

抄録

Matrix proteases are involved in the destruction and degeneration of articular cartilage, which is one of the pathological conditions of osteoarthritis of the temporomandibular joint (TMJOA). We investigated the expression of matrix proteases in combination with IL-1β and cyclic compression loading on three-dimensional (3D) cultured tissues of human articular chondrocytes. Human articular chondrocytes were seeded in atelocollagen sponge and cultured in 3D. Cyclic compressive loading of 40kPa at 0.5Hz was applied to the constructs for 1h, with or without the administration of IL-1β, which was added at concentrations of 0.1, 1 and 10ng/mL. After 6 or 12h of cyclic compression loading, the gene expression of the matrix proteases were evaluated by qRT-PCR. We found that cyclic compression loading significantly increased the expression of MMP-3, ADAMTS-4 and ADAM-17, while IL-1β stimulation significantly increased the expression of MMP-3, MMP-13, ADAMTS-4, ADAMTS-5 and ADAM-17. The expression of MMP-3 was synergistically upregulated by combining cyclic compressive loading with IL-1β when compared with a single stimulation. Therefore we believe that the application of our present biomechanical and biochemical model, which mimics the human intra-articular environment of OA, can facilitate elucidation of the mechanisms of articular cartilage degeneration and destruction in TMJOA. (J Osaka Dent Univ 2021; 55: 91-98)