Role of Cartilage Degrading Enzymes and their End products in the Pathogenesis of Inflammatory Arthritis

Arthritis is a multifactorial degenerative disease of the joints marked with articular cartilage degradation and is characterized by a sequence of molecular events leading to irreversible damage. Cartilage, which is actually a dynamic structure made up of proteins and proteoglycans, interacts with chondrocytes and conduct signals through feedback loops to control the behavior of the chondrocytes. However, an imbalance in the metabolism of extracellular matrix (ECM) components or an error in gene expression, transcription, translation, or posttranslational modification would end up in altered homeostasis of the cartilage leading to the joint pathology. Degradation of the cartilage is believed to be principally mediated by proteases and glycosidases particularly matrix metalloproteases (MMPs), aggrecanases and hyaluronidases. MMPs degrade collagen of ECM while, aggrecanases cleave proteoglycan aggrecan. The major substrates for glycosidases are hyaluronan and other glycosaminoglycans, which serve as lubricants at the joint and also regulate the expression and functioning of MMPs. The molecular expression and regulation of these enzymes are thus shown to be critical in arthritis perpetuation and therefore have emerged as potent therapeutic targets in the management of arthritis. In view of this, the present review focus on the involvement of cartilage degrading enzymes and cartilage degradation products in arthritis pathophysiology.