Combined effects of tumor necrosis factor-α and interleukin-1β on lysyl oxidase and matrix metalloproteinase expression in human knee synovial fibroblasts in vitro

Previous studies have demonstrated that inflammatory cytokines are associated with matrix metalloproteinases (MMPs) and/or lysyl oxidases (LOXs) produced by anterior cruciate ligament (ACL) fibroblasts, which may contribute to the poor healing ability of the ACL. To evaluate whether the synovium also participates in ACL healing, the inflammatory microenvironment of the knee joint cavity was mimicked following ACL injury, and the combined effects of tumor necrosis factor-alpha (TNF-alpha) and interleukin-1 beta (IL-1 beta) on the expression of MMPs and LOXs in synovial fibroblasts were studied. Cell viability was evaluated using trypan blue staining in the presence of TNF-alpha and IL-1 beta, and the expression of LOXs and MMPs was measured by reverse transcription-quantitative polymerase chain reaction. MMP-2 activity was also measured by zymography. The results indicated that the combined effects of TNF-alpha and IL-1 beta inhibited LOX expression, while promoting MMP-1, -2 and -3 expression and MMP-2 activity in synovial fibroblasts. These changes may impede healing by altering the balance between the degradative and biosynthetic arms of the ligament tissue remodeling process. Collectively, the present results suggest that the poor healing ability of cruciate ligaments may be due to the sensitivity of the synovium to inflammatory factors. Therefore, the synovium potentially serves a key regulatory role in the joint cavity microenvironment and in the healing process of the ACL, and thus should be considered as a therapeutic target to aid in the treatment of patients with ACL trauma.