Differential MMP-2 activity induced by mechanical compression and inflammatory factors in human synoviocytes

The anterior cruciate ligament, posterior cruciate ligament, cartilage and meniscus in human knee joint have poor healing ability. Accumulation of MMPs in the joint fluids due to knee injury has been considered as the main reason. Our previous experiments showed that synovium may be the major regulator of MMPs in joint cavity after injury. In this paper, we used human synoviocytes harvested from synovium to determine whether mechanical injury and inflammatory factors will induce MMP-2 production in synoviocytes. With zymography, we found that mechanical compression increased the MMP-2 production by 23% under 6% compressions, 61% under 12% compression and 109% under 14% compressions. In addition, TNF-alpha can also elevate the activity of MMP-2 in a dose dependent manner, while IL-1alpha does not. However, mixture of these two factors dramatically increased MMP-2 production by 201%. In addition, mechanical injury had a strong synergistic effect on MMP-2 production with TNF-alpha, IL-1alpha and their mixture, increasing by 207%, 354% and 468% individually. The generic MMP activity assayrevealed that mechanical compression increased the generic activity. APMA treatment increased the generic activity of MMPs induced by compres-