We sought to determine the molecular basis for the anticatabolic effects of mechanical signals on fibrocartilage cells by studying the expression of a variety of matrix metalloproteinases (MMPs). Furthermore, we examined whether the effects of biomechanical strain on MMP gene expression are sustained.
Fibrochondrocytes from temporomandibular joint (TMJ) discs were exposed to dynamic tensile strain for various time intervals in the presence of interleukin (IL)-1beta. The regulation of the messenger RNA (mRNA) expression and synthesis of MMPs and tissue inhibitors of MMPs (TIMPs) were examined by end-point and real-time reverse transcriptase-polymerase chain reaction (RT-PCR) as well as Western blot analysis.
Fibrochondrocytes expressed mRNA for MMP-2, -3, -7, -8, -9, -11, -13, -14, -16, -17, and -19 as well as TIMP-1, -2, and -3, IL-1beta induced a significant (P<0.05) upregulation of mRNA for MMP-3, -7, -8, -9, -13, -16, -17, and -19. The IL-1beta-stimulated upregulation of these MMPs was significantly (P<0.05) abrogated by dynamic tensile strain. However, MMP-2, -11, -14, and TIMPs were not affected by either IL-1beta or tensile strain. Biomechanical strain also inhibited the IL-1beta-stimulated protein synthesis of MMP-3, -7, -8, -9, -13, -16, and -17. Application of mechanical strain for various time intervals during a 24-h incubation with IL-1beta showed that the suppressive effects of mechanical signals are sustained.
The data provide evidence that biomechanical signals can downregulate the catabolic activity of fibrocartilage cells in an inflammatory environment by inhibiting the expression of a variety of MMPs. Furthermore, the matrix-protective effects of biomechanical signals are sustained even in an inflammatory environment.