Temporospatial production of reactive oxygen species in articular chondrocytes is induced by the endocytosis of fibronectin fragments, alpha 5 beta 1 integrin and NADPH oxidase 2

Abstract

Purpose: Fibronectin fragments (FN-f) found in OA cartilage and synovial fluid have been used as an in vitro model of OA and can contribute to OA progression in vivo. FN-f, but not intact FN, induces a catabolic response by chondrocytes that includes production of pro-inflammatory mediators and MMPs including MMP-13. How cells sense and respond to a damaged ECM containing fragmented proteins is not understood and is a focus of our investigations. We previously showed that FN-f induction of MMP-13 requires NADPH oxidase (Nox 2) production of reactive oxygen species (ROS) which act as second messengers by activating MAP kinase signaling.