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. 1988 Oct;47(10):801–808. doi: 10.1136/ard.47.10.801

Activation of neutral metalloprotease in human osteoarthritic knee cartilage: evidence for degradation in the core protein of sulphated proteoglycan.

J Martel-Pelletier 1, J P Pelletier 1, C J Malemud 1
PMCID: PMC1003607  PMID: 3196082

Abstract

The neutral, metal dependent, proteoglycan degrading enzymes (NMPEs) in human osteoarthritic knee cartilage homogenates were activated by p-aminophenylmercuric acetate (APMA). The resultant effect on the structure of newly synthesised and already existing sulphated proteoglycan was measured. Newly synthesised and already existing proteoglycan aggregated to hyaluronic acid was reduced (p less than 0.01, p less than 0.05 respectively) when measured by chromatography on Sepharose CL-2B eluted with associative buffer. The APMA activated enzyme affected both the newly synthesised and already existing proteoglycan aggregate similarly (r = 0.79, p less than 0.001). Treatment of cartilage homogenates with APMA and 1,10-phenanthroline (10 mM) showed that the amount of aggregated proteoglycan was at the control level. The hydrodynamic size of the proteoglycan monomer (A1D1) was also reduced by treatment of cartilage homogenates with APMA. Reaggregation experiments with fraction A1D1 and exogenous hyaluronic acid and link protein showed a similar defect in forming proteoglycan aggregates. These data showed that activation of the NMPEs altered the structure of proteoglycan in two ways. The most consistent change was a reduction in the ability of proteoglycan to form aggregates with hyaluronic acid. This was likely to have occurred via a cleavage of the core protein in or around the hyaluronic acid binding globular domain. A second alteration probably includes a limited proteolytic cleavage in the remainder of the core protein.

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Selected References

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  1. BITTER T., MUIR H. M. A modified uronic acid carbazole reaction. Anal Biochem. 1962 Oct;4:330–334. doi: 10.1016/0003-2697(62)90095-7. [DOI] [PubMed] [Google Scholar]
  2. Campbell I. K., Roughley P. J., Mort J. S. The action of human articular-cartilage metalloproteinase on proteoglycan and link protein. Similarities between products of degradation in situ and in vitro. Biochem J. 1986 Jul 1;237(1):117–122. doi: 10.1042/bj2370117. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Doherty M., Watt I., Dieppe P. Influence of primary generalised osteoarthritis on development of secondary osteoarthritis. Lancet. 1983 Jul 2;2(8340):8–11. doi: 10.1016/s0140-6736(83)90003-x. [DOI] [PubMed] [Google Scholar]
  4. Goldberg V. M., Norby D. P., Sachs B. L., Moskowitz R. W., Malemud C. J. Correlation of histopathology and sulfated proteoglycans in human osteoarthritic hip cartilage. J Orthop Res. 1984;1(3):302–312. doi: 10.1002/jor.1100010310. [DOI] [PubMed] [Google Scholar]
  5. Hardingham T. E., Muir H. Hyaluronic acid in cartilage and proteoglycan aggregation. Biochem J. 1974 Jun;139(3):565–581. doi: 10.1042/bj1390565. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Harmand M. F., Duphil R., Blanquet P. Proteoglycan synthesis in chondrocyte cultures from osteoarthrotic and normal human articular cartilage. Biochim Biophys Acta. 1982 Aug 6;717(2):190–202. doi: 10.1016/0304-4165(82)90169-6. [DOI] [PubMed] [Google Scholar]
  7. Hascall V. C., Heinegård D. Aggregation of cartilage proteoglycans. I. The role of hyaluronic acid. J Biol Chem. 1974 Jul 10;249(13):4232–4241. [PubMed] [Google Scholar]
  8. Malemud C. J., Norby D. P., Sokoloff L. Explant culture of human and rabbit articular chondrocytes. Connect Tissue Res. 1978;6(3):171–179. doi: 10.3109/03008207809152628. [DOI] [PubMed] [Google Scholar]
  9. Malemud C. J., Yoo J. U., Goldberg V. M., Kresina T. F. Structural characteristics of articular cartilage proteoglycan in IgG induced experimental immune synovitis. Ann Rheum Dis. 1987 Jul;46(7):520–526. doi: 10.1136/ard.46.7.520. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Mankin H. J., Dorfman H., Lippiello L., Zarins A. Biochemical and metabolic abnormalities in articular cartilage from osteo-arthritic human hips. II. Correlation of morphology with biochemical and metabolic data. J Bone Joint Surg Am. 1971 Apr;53(3):523–537. [PubMed] [Google Scholar]
  11. Mankin H. J., Lippiello L. The glycosaminoglycans of normal and arthritic cartilage. J Clin Invest. 1971 Aug;50(8):1712–1719. doi: 10.1172/JCI106660. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Martel-Pelletier J., Pelletier J. P., Cloutier J. M., Howell D. S., Ghandur-Mnaymneh L., Woessner J. F., Jr Neutral proteases capable of proteoglycan digesting activity in osteoarthritic and normal human articular cartilage. Arthritis Rheum. 1984 Mar;27(3):305–312. doi: 10.1002/art.1780270310. [DOI] [PubMed] [Google Scholar]
  13. Martel-Pelletier J., Pelletier J. P., Cloutier J. M., Malemud C. J. Newly synthesized and endogenous proteoglycans in human osteoarthritic knee cartilage. J Rheumatol. 1987 Apr;14(2):321–328. [PubMed] [Google Scholar]
  14. Martel-Pelletier J., Pelletier J. P. Neutral metalloproteases and age related changes in human articular cartilage. Ann Rheum Dis. 1987 May;46(5):363–369. doi: 10.1136/ard.46.5.363. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Meachim G. Light microscopy of Indian ink preparations of fibrillated cartilage. Ann Rheum Dis. 1972 Nov;31(6):457–464. doi: 10.1136/ard.31.6.457. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Nojima T., Towle C. A., Mankin H. J., Treadwell B. V. Secretion of higher levels of active proteoglycanases from human osteoarthritic chondrocytes. Arthritis Rheum. 1986 Feb;29(2):292–295. doi: 10.1002/art.1780290219. [DOI] [PubMed] [Google Scholar]
  17. Oegema T. R., Jr, Hascall V. C., Dziewiatkowski D. D. Isolation and characterization of proteoglycans from the swarm rat chondrosarcoma. J Biol Chem. 1975 Aug 10;250(15):6151–6159. [PubMed] [Google Scholar]
  18. Ohno H., Blackwell J., Jamieson A. M., Carrino D. A., Caplan A. I. Calibration of the relative molecular mass of proteoglycan subunit by column chromatography on Sepharose CL-2B. Biochem J. 1986 Apr 15;235(2):553–557. doi: 10.1042/bj2350553. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Palmoski M., Brandt K. Hyaluronate-binding by proteoglycans. Comparison of mildly and severely osteoarthritic regions of human femoral cartilage. Clin Chim Acta. 1976 Jul 1;70(1):87–95. doi: 10.1016/0009-8981(76)90008-5. [DOI] [PubMed] [Google Scholar]
  20. Pelletier J. P., Martel-Pelletier J., Cloutier J. M., Woessner J. F., Jr Proteoglycan-degrading acid metalloprotease activity in human osteoarthritic cartilage, and the effect of intraarticular steroid injections. Arthritis Rheum. 1987 May;30(5):541–548. doi: 10.1002/art.1780300508. [DOI] [PubMed] [Google Scholar]
  21. Pelletier J. P., Martel-Pelletier J., Ghandur-Mnaymneh L., Howell D. S., Woessner J. F., Jr Role of synovial membrane inflammation in cartilage matrix breakdown in the Pond-Nuki dog model of osteoarthritis. Arthritis Rheum. 1985 May;28(5):554–561. doi: 10.1002/art.1780280515. [DOI] [PubMed] [Google Scholar]
  22. Pelletier J. P., Martel-Pelletier J., Howell D. S., Ghandur-Mnaymneh L., Enis J. E., Woessner J. F., Jr Collagenase and collagenolytic activity in human osteoarthritic cartilage. Arthritis Rheum. 1983 Jan;26(1):63–68. doi: 10.1002/art.1780260110. [DOI] [PubMed] [Google Scholar]
  23. Pelletier J. P., Martel-Pelletier J., Malemud C. J. Canine osteoarthritis: effects of endogenous neutral metalloproteoglycanases on articular cartilage proteoglycans. J Orthop Res. 1988;6(3):379–388. doi: 10.1002/jor.1100060309. [DOI] [PubMed] [Google Scholar]
  24. Roughley P. J. Changes in cartilage proteoglycan structure during ageing: origin and effects--a review. Agents Actions Suppl. 1986;18:19–29. doi: 10.1007/978-3-0348-7684-1_3. [DOI] [PubMed] [Google Scholar]
  25. Roughley P. J., White R. J. Age-related changes in the structure of the proteoglycan subunits from human articular cartilage. J Biol Chem. 1980 Jan 10;255(1):217–224. [PubMed] [Google Scholar]
  26. Sandy J. D., Flannery C. R., Plaas A. H. Structural studies on proteoglycan catabolism in rabbit articular cartilage explant cultures. Biochim Biophys Acta. 1987 Dec 10;931(3):255–261. doi: 10.1016/0167-4889(87)90214-x. [DOI] [PubMed] [Google Scholar]
  27. Sapolsky A. I., Howell D. S. Further characterization of a neutral metalloprotease isolated from human articular cartilage. Arthritis Rheum. 1982 Aug;25(8):981–988. doi: 10.1002/art.1780250811. [DOI] [PubMed] [Google Scholar]
  28. Sapolsky A. I., Keiser H., Howell D. S., Woessner J. F., Jr Metalloproteases of human articular cartilage that digest cartilage proteoglycan at neutral and acid pH. J Clin Invest. 1976 Oct;58(4):1030–1041. doi: 10.1172/JCI108526. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Sapolsky A. I., Malemud C. J., Norby D. P., Moskowitz R. W., Matsuta K., Howell D. S. Neutral proteinases from articular chondrocytes in culture. 2. Metal-dependent latent neutral proteoglycanase, and inhibitory activity. Biochim Biophys Acta. 1981 Mar 13;658(1):138–147. doi: 10.1016/0005-2744(81)90257-6. [DOI] [PubMed] [Google Scholar]
  30. Woessner J. F., Jr, Selzer M. G. Two latent metalloproteases of human articular cartilage that digest proteoglycan. J Biol Chem. 1984 Mar 25;259(6):3633–3638. [PubMed] [Google Scholar]
  31. Yanagishita M., Rodbard D., Hascall V. C. Isolation and characterization of proteoglycans from porcine ovarian follicular fluid. J Biol Chem. 1979 Feb 10;254(3):911–920. [PubMed] [Google Scholar]

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