Objectives: This in vitro study was performed to: identify MMPs and tissue inhibitors of MMPs (TIMPs) expressed in FC; analyze if the MMP and TIMP expression is regulated by interleukin (IL)-1beta, the major mediator in arthritis; determine if biomechanical forces can counteract IL-1beta effects on the expression of MMPs and TIMPs.
Methods: FC were obtained from Sprague Dawley rats and subjected to equibiaxial cyclic tensile strain (CTS) using a FX-4000T Flexercell System in the presence or absence of IL-1beta for 4 and 24h. Unstretched FC were also cultured in the presence or absence of IL-1beta. MMP and TIMP expression was analyzed by semi-quantitive RT-PCR.
Results: FC constitutively expressed MMP-1,-2,-3,-9,-11,-14,-16,-17,-19,-24,-25, and TIMP-1,-2,-3. MMP-1,-3,-9,-13, and -19 expression was upregulated in IL-1beta-stimulated cells at 4 and 24h. CTS applied simultaneously to IL-1beta-stimulated FC abrogated the IL-1beta-induced upregulation of MMP-1,-9, and -13. In addition, IL-1beta-stimulated FC subjected to CTS expressed higher levels of TIMPs than unstretched cells incubated with IL-1beta.
Conclusions: Fibrocartilaginous cells from TMJ discs express a variety of matrix-degrading enzymes, but also their inhibitors, suggesting that these cells participate in joint tissue homeostasis. As IL-1beta upregulates synthesis of catabolic MMPs, it is suggested that FC can contribute to cartilage and fibrocartilage degradation in arthritic TMJ. Finally, biomechanical forces of physiological levels might protect against extracellular matrix degradation by abrogating the catabolic effects of IL-1beta in inflamed TMJ.
7R01AT000646-05 and 5R01DE015399-03