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Annals of the Rheumatic Diseases logoLink to Annals of the Rheumatic Diseases
. 1994 Jan;53(1):8–13. doi: 10.1136/ard.53.1.8

Release of cartilage oligomeric matrix protein (COMP) into joint fluid after knee injury and in osteoarthritis.

L S Lohmander 1, T Saxne 1, D K Heinegård 1
PMCID: PMC1005235  PMID: 8311563

Abstract

OBJECTIVE--The release of fragments of cartilage oligomeric matrix protein (COMP) and aggrecan into knee joint fluid and serum after joint injury and in post-traumatic and primary osteoarthritis was monitored in a cross-sectional study. METHODS--Samples of joint fluid and serum were obtained from healthy volunteers and from patients with arthroscopically verified injury to anterior cruciate ligament and or meniscus of the knee at different times after injury and with different degrees of post-traumatic osteoarthritis. Samples were also obtained from patients with primary osteoarthritis. Fragments of COMP were quantified in joint fluid and in serum by enzyme-linked immunoassay. Fragments of aggrecan were quantified in joint fluid by enzyme-linked immunoassay. RESULTS--Concentrations of COMP and aggrecan fragments in joint fluid in the study groups were increased over the reference levels of 47 (range 10-109) and 34 (range 6-59) micrograms/mL, respectively, in the volunteers with healthy knees. The ratios (w/w) of aggrecan to COMP fragments in joint fluid were also increased in all study groups over that in the reference group. Average concentrations of COMP in joint fluid were high shortly after injury and decreased with time but remained increased over reference levels for many years. Joint fluid COMP concentrations were also increased in early stage post-traumatic and primary osteoarthritis, but not in advanced osteoarthritis. CONCLUSION--Increased amounts of aggrecan and COMP fragments are released into joint fluid after joint injury and in early stage osteoarthritis. The ratios of aggrecan to COMP in joint fluid vary with time after injury and with osteoarthritis disease stage. Although both molecules are sensitive to the agents active in matrix breakdown in joint disease, differences may thus exist in the release mechanisms and attempted repair. The concentrations of the individual markers in body fluids and their ratios may serve to monitor treatment efficacy, disease progression and repair in osteoarthritis and other joint diseases.

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Selected References

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  1. Dahlberg L., Ryd L., Heinegård D., Lohmander L. S. Proteoglycan fragments in joint fluid. Influence of arthrosis and inflammation. Acta Orthop Scand. 1992 Aug;63(4):417–423. doi: 10.3109/17453679209154758. [DOI] [PubMed] [Google Scholar]
  2. Dodge G. R., Poole A. R. Immunohistochemical detection and immunochemical analysis of type II collagen degradation in human normal, rheumatoid, and osteoarthritic articular cartilages and in explants of bovine articular cartilage cultured with interleukin 1. J Clin Invest. 1989 Feb;83(2):647–661. doi: 10.1172/JCI113929. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Fife R. S., Brandt K. D., Braunstein E. M., Myers S. L., Katz B. P., Ehlich J., Shelbourne K. D., Kalasinski L. A. The presence of cartilage matrix glycoprotein in serum as determined by immunolocation analysis is not a sensitive indicator of "early" osteoarthritis of the knee. J Lab Clin Med. 1991 Apr;117(4):332–338. [PubMed] [Google Scholar]
  4. Fife R. S. Identification of cartilage matrix glycoprotein in synovial fluid in human osteoarthritis. Arthritis Rheum. 1988 Apr;31(4):553–556. doi: 10.1002/art.1780310414. [DOI] [PubMed] [Google Scholar]
  5. Forslind K., Eberhardt K., Jonsson A., Saxne T. Increased serum concentrations of cartilage oligomeric matrix protein. A prognostic marker in early rheumatoid arthritis. Br J Rheumatol. 1992 Sep;31(9):593–598. doi: 10.1093/rheumatology/31.9.593. [DOI] [PubMed] [Google Scholar]
  6. Geborek P., Saxne T., Heinegård D., Wollheim F. A. Measurement of synovial fluid volume using albumin dilution upon intraarticular saline injection. J Rheumatol. 1988 Jan;15(1):91–94. [PubMed] [Google Scholar]
  7. Hedbom E., Antonsson P., Hjerpe A., Aeschlimann D., Paulsson M., Rosa-Pimentel E., Sommarin Y., Wendel M., Oldberg A., Heinegård D. Cartilage matrix proteins. An acidic oligomeric protein (COMP) detected only in cartilage. J Biol Chem. 1992 Mar 25;267(9):6132–6136. [PubMed] [Google Scholar]
  8. Heinegård D., Oldberg A. Structure and biology of cartilage and bone matrix noncollagenous macromolecules. FASEB J. 1989 Jul;3(9):2042–2051. doi: 10.1096/fasebj.3.9.2663581. [DOI] [PubMed] [Google Scholar]
  9. Heinegård D., Saxne T. Molecular markers of processes in cartilage in joint disease. Br J Rheumatol. 1991;30 (Suppl 1):21–24. [PubMed] [Google Scholar]
  10. Lohmander L. S., Dahlberg L., Ryd L., Heinegård D. Increased levels of proteoglycan fragments in knee joint fluid after injury. Arthritis Rheum. 1989 Nov;32(11):1434–1442. doi: 10.1002/anr.1780321113. [DOI] [PubMed] [Google Scholar]
  11. Lohmander L. S., Hoerrner L. A., Dahlberg L., Roos H., Björnsson S., Lark M. W. Stromelysin, tissue inhibitor of metalloproteinases and proteoglycan fragments in human knee joint fluid after injury. J Rheumatol. 1993 Aug;20(8):1362–1368. [PubMed] [Google Scholar]
  12. Lohmander L. S., Hoerrner L. A., Lark M. W. Metalloproteinases, tissue inhibitor, and proteoglycan fragments in knee synovial fluid in human osteoarthritis. Arthritis Rheum. 1993 Feb;36(2):181–189. doi: 10.1002/art.1780360207. [DOI] [PubMed] [Google Scholar]
  13. Lohmander L. S., Lark M. W., Dahlberg L., Walakovits L. A., Roos H. Cartilage matrix metabolism in osteoarthritis: markers in synovial fluid, serum, and urine. Clin Biochem. 1992 Jun;25(3):167–174. doi: 10.1016/0009-9120(92)90250-v. [DOI] [PubMed] [Google Scholar]
  14. Lohmander L. S. Markers of cartilage metabolism in arthrosis. A review. Acta Orthop Scand. 1991 Dec;62(6):623–632. doi: 10.3109/17453679108994513. [DOI] [PubMed] [Google Scholar]
  15. Messner K., Gillquist J., Björnsson S., Lohmander L. S. Proteoglycan fragments in rabbit joint fluid correlated to arthrosis stage. Acta Orthop Scand. 1993 Jun;64(3):312–316. doi: 10.3109/17453679308993633. [DOI] [PubMed] [Google Scholar]
  16. Mörgelin M., Heinegård D., Engel J., Paulsson M. Electron microscopy of native cartilage oligomeric matrix protein purified from the Swarm rat chondrosarcoma reveals a five-armed structure. J Biol Chem. 1992 Mar 25;267(9):6137–6141. [PubMed] [Google Scholar]
  17. Oldberg A., Antonsson P., Lindblom K., Heinegård D. COMP (cartilage oligomeric matrix protein) is structurally related to the thrombospondins. J Biol Chem. 1992 Nov 5;267(31):22346–22350. [PubMed] [Google Scholar]
  18. Sandy J. D., Flannery C. R., Neame P. J., Lohmander L. S. The structure of aggrecan fragments in human synovial fluid. Evidence for the involvement in osteoarthritis of a novel proteinase which cleaves the Glu 373-Ala 374 bond of the interglobular domain. J Clin Invest. 1992 May;89(5):1512–1516. doi: 10.1172/JCI115742. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Saxne T., Glennås A., Kvien T. K., Melby K., Heinegård D. Release of cartilage macromolecules into the synovial fluid in patients with acute and prolonged phases of reactive arthritis. Arthritis Rheum. 1993 Jan;36(1):20–25. doi: 10.1002/art.1780360105. [DOI] [PubMed] [Google Scholar]
  20. Saxne T., Heinegård D. Cartilage oligomeric matrix protein: a novel marker of cartilage turnover detectable in synovial fluid and blood. Br J Rheumatol. 1992 Sep;31(9):583–591. doi: 10.1093/rheumatology/31.9.583. [DOI] [PubMed] [Google Scholar]
  21. Saxne T., Heinegård D. Synovial fluid analysis of two groups of proteoglycan epitopes distinguishes early and late cartilage lesions. Arthritis Rheum. 1992 Apr;35(4):385–390. doi: 10.1002/art.1780350404. [DOI] [PubMed] [Google Scholar]
  22. Saxne T., Heinegård D., Wollheim F. A., Pettersson H. Difference in cartilage proteoglycan level in synovial fluid in early rheumatoid arthritis and reactive arthritis. Lancet. 1985 Jul 20;2(8447):127–128. doi: 10.1016/s0140-6736(85)90229-6. [DOI] [PubMed] [Google Scholar]
  23. Saxne T., Heinegård D., Wollheim F. A. Therapeutic effects on cartilage metabolism in arthritis as measured by release of proteoglycan structures into the synovial fluid. Ann Rheum Dis. 1986 Jun;45(6):491–497. doi: 10.1136/ard.45.6.491. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Saxne T., Wollheim F. A., Pettersson H., Heinegård D. Proteoglycan concentration in synovial fluid: predictor of future cartilage destruction in rheumatoid arthritis? Br Med J (Clin Res Ed) 1987 Dec 5;295(6611):1447–1448. doi: 10.1136/bmj.295.6611.1447. [DOI] [PMC free article] [PubMed] [Google Scholar]

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