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In the mid-1990’s the identity of “the Aggrecanases” (i.e. ADAMTS-4 & ADAMTS-5) were first described by researchers at Dupont, USA. Since then there have been numerous studies investigating the unique properties of these two different matrix metalloproteinases that are responsible for aggrecan degradation in the pathogenesis of osteoarthritis (OA) in humans and numerous animal models of the disease. It is clear that both of these “Aggrecanases” can cleave aggrecan in its interglobular domain (IGD) thereby releasing the majority of the glycosaminoglycan containing domains of aggrecan from the cartilage that eventually leads to loss of the cartilage’s physiological function of resisting compressive loading during joint movement; i.e. the degradation of aggrecan by the “Aggrecanases” leads to loss of aggrecan from the cartilage that eventually leads to cartilage fibrillation and eburnation down to the subchondral bone (i.e. joint space narrowing). In spite of the discovery of “the Aggrecanases” now over 15 – 20 years ago, researchers still do not know which of the two “Aggrecanases” (either ADAMTS-4 or -5) is the major contributor to cartilage degradation in the pathogenesis of OA in different animal models of OA and in human patients. Recently, our laboratory discovered a spice-variant of one of the two “Aggrecanases”; the spice-variant of ADAMTS-4 named ADAMTS-4_v1 that is specifically produced in synovial tissue from human OA patients; i.e. this spice-variant is produced only in the synovium and not the cartilage from human OA patients. We believe that this newly discovered synovium-derived “Aggrecanase” is a major contributor to the degradation of aggrecan from the superficial zone of articular cartilage in the early stages of the onset of OA pathology in human patients. These recent findings have provided a new target for pharmaceutical interventions that can be used to slow down the progression of OA in humans.
Reference: Wainwright SD, Bondeson J, Caterson B & Hughes CE (2013). ADAMTS4_v1 is a splice variant of ADAMTS4 that is expressed as a protein in human synovium and cleaves aggrecan at the interglobular domain. Arthritis Rheum. July 29th (Epub ahead of print). | 
