A graphic representation of the generation of pathology-relevant neoepitopes of inflamed joint cartilage. The enzymes presently receiving the most attention are the matrix metalloproteinases (MMPs) and aggrecanases (ADAM-TS (a disintegrin and metalloproteinase with thrombospondin motifs)). The most abundant cartilage proteins are collagen type II and aggrecan. Protease-generated fragments of collagen type II and aggrecan produced through the action of these important enzymes, which may be relevant molecules in tissue destruction, can be used to monitor tissue turnover. These fragments, such as C-terminal telopeptide of type II collagen (CTX-II), may be used in clinical settings, in preclinical models and in simple ex vivo and in vitro systems. Figure adapted with permission from .