Involvement of H-Ras and reactive oxygen species in proinflammatory cytokine-induced matrix metalloproteinase-13 expression in human articular chondrocytes

► H-Ras inhibitors and Ras siRNA suppress IL-1β- and TNF-α-induced MMP-13 expression. ► NADPH oxidase inhibitors reduce superoxide production and MMP-13 induction. ► Antioxidants inhibit cytokine-induced MMP-13 mRNA and protein expression. ► H-Ras and NADPH oxidase-generated ROS are implicated in MMP-13 regulation. ► MMP-13-driven cartilage erosion can be reduced by such inhibitors and antioxidants.