Pathways of aggrecan processing in joint tissues Implications for disease mechanism and monitoring

Aggrecan is an essential matrix constituent of the soft tissues of the joint, which include the articular and meniscal cartilages and the supporting intraarticular ligaments. Our understanding of the pathways of aggrecan turnover in these tissues is limited. However, recent evidence obtained from analysis of human synovial fluids (Sandy et al. 1992, Lohmander et al. 1993), human articular cartilages (Bayne et al. 1995) cartilage explant cultures (Sandy et al. 1991) and chondrocyte cultures (Lark et al. 1995) has suggested a central role for a novel proteoglycan-degrading proteinase (aggrecanase) which cleaves the Glu 373- Ala374 bond within the interglobular domain of aggrecan.