Title : The structure of aggrecan
fragments in human synovial fluid
Abstract :
- Evidence for the involvement in osteoarthritis of a novel proteinase which cleaves the Glu 373-Ala 374 bond of the interglobular domain
- Synovial fluid was collected from patients with recent knee injury and from patients with early or late stage osteoarthritis
- Chondroitin sulfate-substituted aggrecan fragments present in these fluids, and in normal bovine synovial fluid, were purified by cesium chloride gradient centrifugation, enzymically deglycosylated and fractionated by gel filtration on Superose-12
- Each sample contained two major aggrecan core protein populations with apparent molecular masses of approximately 90 kD and 150 kD
- For all samples, NH2-terminal analysis of both populations gave a single major sequence beginning ARGSV
- This NH2 terminus results from cleavage of the human aggrecan core protein at the Glu 373-Ala 374 bond within the interglobular domain between the G1 and G2 domains
- Cleavage at this site also occurs during control and interleukin-1 stimulated aggrecan catabolism in bovine cartilage explant cultures (Sandy, J., P. Neame, R. Boynton, and C. Flannery
- 1991
- J. Biol
- Chem
- 266:8683-8685)
- These results indicate that the major aggrecan fragments present in both osteoarthritic human synovial fluid and in normal bovine synovial fluid are large, being composed of a short NH2-terminal stretch of the interglobular domain , the G2 domain , the keratan sulfate domain , and variable lengths of the chondroitin sulfate domain(s)
- We conclude that the release of aggrecan fragments from articular cartilage into the synovial fluid seen at all stages of human osteoarthritis (Lohmander, L. S. 1991
- Acta Orthop
- Scand
- 62:623-632) is promoted by the action of a normal cartilage proteinase which cleaves the Glu 373-Ala 374 bond of the interglobular domain