TGF-β1 and Mechanical-Stretch Induction of Lysyl-Oxidase and Matrix-Metalloproteinase Expression in Synovial Fibroblasts Requires NF-κB Pathways

Abstract

The imbalance in the expression of matrix metalloproteinases (MMPs) and lysyl oxidases (LOXs) in synovial fibroblasts (SFs) caused by mechanical injury and inflammatory response prevents injured anterior cruciate ligaments (ACLs) from self-healing. However, research on the effect of growth factors on SFs on regulating the microenvironment is limited. In this study, mechanical injury and exogenous transform growth factor-β1 (TGF-β1) were employed to mimic a joint-cavity microenvironment with ACL trauma. The function of the NF-κB transcription factor was further studied. The study found that the gene expression of LOXs (except LOXL-1), MMP-1, -2, and -3 in SFs was promoted by the combination of injurious mechanical stretching and TGF-β1 and that the upregulation of MMPs was higher than that of LOXs. In addition, MMP-2 activity induced by the combination of injurious stretch and TGF-β1 was inhibited by NF-κB inhibitors such as Bay11-7082 and Bay11-7085. The findings concluded that the synovium was an important regulator of the knee joint-cavity microenvironment after ACL injury and that the NF-κB pathway mediated the regulation of MMP-2 in SFs via mechanical factors and TGF-β1.