Deschner J, Rath-Deschner B, Agarwal S
The Ohio State University, Oral Biology and Orthopedics, 4171 Postle Hall, 305 West 12th Avenue, Columbus, OH 43210, USA.
Osteoarthritis Cartilage. 2006 Mar;14(3):264-72. doi: 10.1016/j.joca.2005.09.005. Epub 2005 Nov 14.
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.
通过研究多种基质金属蛋白酶（MMPs）的表达，我们试图确定机械信号对纤维软骨细胞抗分解代谢作用的分子基础。此外，我们还研究了生物力学应变对MMP基因表达的影响是否具有持续性。
在白细胞介素（IL）-1β存在的情况下，将来自颞下颌关节（TMJ）盘的纤维软骨细胞暴露于动态拉伸应变中不同时间间隔。通过终点法和实时逆转录-聚合酶链反应（RT-PCR）以及蛋白质印迹分析，检测MMPs和MMP组织抑制剂（TIMPs）的信使核糖核酸（mRNA）表达及合成的调控情况。
纤维软骨细胞表达MMP-2、-3、-7、-8、-9、-11、-13、-14、-16、-17和-19以及TIMP-1、-2和-3的mRNA，IL-1β诱导MMP-3、-7、-8、-9、-13、-16、-17和-19的mRNA显著（P<0.05）上调。动态拉伸应变显著（P<0.05）消除了IL-1β刺激的这些MMPs上调。然而，MMP-2、-11、-14和TIMPs不受IL-1β或拉伸应变的影响。生物力学应变还抑制了IL-1β刺激的MMP-3、-7、-8、-9、-13、-16和-17的蛋白质合成。在与IL-1β孵育24小时期间施加不同时间间隔的机械应变表明，机械信号的抑制作用具有持续性。
数据表明，生物力学信号可通过抑制多种MMPs的表达，在炎症环境中下调纤维软骨细胞的分解代谢活性。此外，即使在炎症环境中，生物力学信号的基质保护作用也具有持续性。
