Lysyl oxidase is involved in synovial hyperplasia and angiogenesis in rats with collagen-induced arthritis

Abstract

Lysyl oxidase (LOX) serves an important role in remodeling the extracellular matrix and angiogenesis in various types of cancer; however, whether LOX is involved in the pathogenesis of rheumatoid arthritis remains unknown. In order to investigate this in the present study, β-aminopropionitrile, an inhibitor of LOX, was injected intraperitoneally into rats with type II collagen-induced arthritis (CIA). Subsequently, synovial hyperplasia was examined by hematoxyl in and eosin staining, and the microvascular density (MVD) and expression levels of LOX, matrix metalloproteinase (MMP)-2 and MMP-9 in the synovial membrane and fluid were determined by immunohistochemistry and ELISA, respectively. The enzyme activity of LOX was evaluated by the Amplex Red Hydrogen Peroxide method. The results demonstrated an increased amount of rough synovial membranes, higher MVD in these membranes and more synovial cell layers in CIA rats compared with in the control rats. In addition, higher enzymatic activity of LOX and higher expression levels of MMP-2 and MMP-9 were revealed in CIA rats compared with in the control rats. Notably, β-aminopropionitrile inhibited paw swelling and the decreased the arthritis index, the MVD in the synovial membranes and the expression levels of MMP-2 and MMP-9. Furthermore, the expression level of LOX in the synovial membranes was positively associated with the MVD and the expression levels of MMP-2 and MMP-9, suggesting that LOX promotes synovial hyperplasia and angiogenesis and that LOX may be a potential therapeutic target for rheumatoid arthritis.