Enzyme degradation products in human intervertebral disc

Abstract

Loss of proteoglycan is a common finding in degeneration of the intervertebral disc, leading to a decreased swelling pressure and impaired mechanical functioning. In addition, the aggrecan population is known to be particularly fragmented and less able to aggregate in comparison to those found in, for example, articular cartilage. There is biochemical evidence that the protein core of disc aggrecan is broken down by both aggrecanase and matrix metalloproteinases (MMPs) in human intervertebral disc (Strolovics et al. 1997). We have studied the activity and location of these groups of enzymes in intervertebral discs of varying degrees of degeneration using the monoclonal antibodies BC3 and 13 to demonstrate aggrecanase actvity and BC4 and 14 to demonstrate MMP activity. These antibodies recognise the neoepitope created by enzyme cleavage: BC3 and 14 the N-terminus (ARGSV-and FFGVG-, respectively) and BC13 and 4 the C-terminus (– NITEGE and -DIPEN, respectively; Caterson et al. 1995).