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Annals of the Rheumatic Diseases logoLink to Annals of the Rheumatic Diseases
. 2002 Nov;61(Suppl 2):ii78–ii81. doi: 10.1136/ard.61.suppl_2.ii78

Type II collagen degradation and its regulation in articular cartilage in osteoarthritis

A Poole, M Kobayashi, T Yasuda, S Laverty, F Mwale, T Kojima, T Sakai, C Wahl, S El-Maadawy, G Webb, E Tchetina, W Wu
PMCID: PMC1766700  PMID: 12379630

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Figure 1 .

Figure 1

Diagrammatic representation of some of the elements of cartilage structure and matrix turnover. Type II collagen fibrils form an endoskeleton and associated with them in interfibrillar sites resides the proteoglycan aggrecan aggregated with hyaluronic acid. In physiology there is active pericellular turnover of extracellular matrix involving proteolysis mediated by matrix metalloproteinases (MMPs). In OA there is increased damage to resident matrix molecules more remote from chondrocytes with up regulation of synthesis of collagen and proteoglycan. These new molecules are also subject to degradation. Degradation products are released to body fluids where they can be detected. Increased proteolysis involves up regulation of interleukin (IL)1 and tumour necrosis factor ß (TNFß) expression by chondrocytes, nitric oxide (NO) production, and receptor activation by matrix degradation products, which is IL1 and TNFα dependent. Reproduced with permission from references 35 and 36.

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Attur M. G., Dave M., Cipolletta C., Kang P., Goldring M. B., Patel I. R., Abramson S. B., Amin A. R. Reversal of autocrine and paracrine effects of interleukin 1 (IL-1) in human arthritis by type II IL-1 decoy receptor. Potential for pharmacological intervention. J Biol Chem. 2000 Dec 22;275(51):40307–40315. doi: 10.1074/jbc.M002721200. [DOI] [PubMed] [Google Scholar]
  2. Bashir A., Gray M. L., Burstein D. Gd-DTPA2- as a measure of cartilage degradation. Magn Reson Med. 1996 Nov;36(5):665–673. doi: 10.1002/mrm.1910360504. [DOI] [PubMed] [Google Scholar]
  3. Billinghurst R. C., Dahlberg L., Ionescu M., Reiner A., Bourne R., Rorabeck C., Mitchell P., Hambor J., Diekmann O., Tschesche H. Enhanced cleavage of type II collagen by collagenases in osteoarthritic articular cartilage. J Clin Invest. 1997 Apr 1;99(7):1534–1545. doi: 10.1172/JCI119316. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Dahlberg L., Billinghurst R. C., Manner P., Nelson F., Webb G., Ionescu M., Reiner A., Tanzer M., Zukor D., Chen J. Selective enhancement of collagenase-mediated cleavage of resident type II collagen in cultured osteoarthritic cartilage and arrest with a synthetic inhibitor that spares collagenase 1 (matrix metalloproteinase 1). Arthritis Rheum. 2000 Mar;43(3):673–682. doi: 10.1002/1529-0131(200003)43:3<673::AID-ANR25>3.0.CO;2-8. [DOI] [PubMed] [Google Scholar]
  5. Goldring M. B. The role of the chondrocyte in osteoarthritis. Arthritis Rheum. 2000 Sep;43(9):1916–1926. doi: 10.1002/1529-0131(200009)43:9<1916::AID-ANR2>3.0.CO;2-I. [DOI] [PubMed] [Google Scholar]
  6. Hashimoto S., Ochs R. L., Komiya S., Lotz M. Linkage of chondrocyte apoptosis and cartilage degradation in human osteoarthritis. Arthritis Rheum. 1998 Sep;41(9):1632–1638. doi: 10.1002/1529-0131(199809)41:9<1632::AID-ART14>3.0.CO;2-A. [DOI] [PubMed] [Google Scholar]
  7. Hollander A. P., Heathfield T. F., Webber C., Iwata Y., Bourne R., Rorabeck C., Poole A. R. Increased damage to type II collagen in osteoarthritic articular cartilage detected by a new immunoassay. J Clin Invest. 1994 Apr;93(4):1722–1732. doi: 10.1172/JCI117156. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Hollander A. P., Pidoux I., Reiner A., Rorabeck C., Bourne R., Poole A. R. Damage to type II collagen in aging and osteoarthritis starts at the articular surface, originates around chondrocytes, and extends into the cartilage with progressive degeneration. J Clin Invest. 1995 Dec;96(6):2859–2869. doi: 10.1172/JCI118357. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Homandberg G. A., Hui F. High concentrations of fibronectin fragments cause short-term catabolic effects in cartilage tissue while lower concentrations cause continuous anabolic effects. Arch Biochem Biophys. 1994 Jun;311(2):213–218. doi: 10.1006/abbi.1994.1229. [DOI] [PubMed] [Google Scholar]
  10. Kempson G. E. Relationship between the tensile properties of articular cartilage from the human knee and age. Ann Rheum Dis. 1982 Oct;41(5):508–511. doi: 10.1136/ard.41.5.508. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Kojima T., Mwale F., Yasuda T., Girard C., Poole A. R., Laverty S. Early degradation of type IX and type II collagen with the onset of experimental inflammatory arthritis. Arthritis Rheum. 2001 Jan;44(1):120–127. doi: 10.1002/1529-0131(200101)44:1<120::AID-ANR16>3.0.CO;2-X. [DOI] [PubMed] [Google Scholar]
  12. Lark M. W., Bayne E. K., Flanagan J., Harper C. F., Hoerrner L. A., Hutchinson N. I., Singer I. I., Donatelli S. A., Weidner J. R., Williams H. R. Aggrecan degradation in human cartilage. Evidence for both matrix metalloproteinase and aggrecanase activity in normal, osteoarthritic, and rheumatoid joints. J Clin Invest. 1997 Jul 1;100(1):93–106. doi: 10.1172/JCI119526. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Manicourt D. H., Lenz M. E., Thonar E. J. Levels of serum keratan sulfate rise rapidly and remain elevated following anterior cruciate ligament transection in the dog. J Rheumatol. 1991 Dec;18(12):1872–1876. [PubMed] [Google Scholar]
  14. Mwale Fackson, Tchetina Elena, Wu C. William, Poole A. Robin. The assembly and remodeling of the extracellular matrix in the growth plate in relationship to mineral deposition and cellular hypertrophy: an in situ study of collagens II and IX and proteoglycan. J Bone Miner Res. 2002 Feb;17(2):275–283. doi: 10.1359/jbmr.2002.17.2.275. [DOI] [PubMed] [Google Scholar]
  15. Nelson F., Dahlberg L., Laverty S., Reiner A., Pidoux I., Ionescu M., Fraser G. L., Brooks E., Tanzer M., Rosenberg L. C. Evidence for altered synthesis of type II collagen in patients with osteoarthritis. J Clin Invest. 1998 Dec 15;102(12):2115–2125. doi: 10.1172/JCI4853. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Neuhold L. A., Killar L., Zhao W., Sung M. L., Warner L., Kulik J., Turner J., Wu W., Billinghurst C., Meijers T. Postnatal expression in hyaline cartilage of constitutively active human collagenase-3 (MMP-13) induces osteoarthritis in mice. J Clin Invest. 2001 Jan;107(1):35–44. doi: 10.1172/JCI10564. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Poole A. R., Rizkalla G., Ionescu M., Reiner A., Brooks E., Rorabeck C., Bourne R., Bogoch E. Osteoarthritis in the human knee: a dynamic process of cartilage matrix degradation, synthesis and reorganization. Agents Actions Suppl. 1993;39:3–13. doi: 10.1007/978-3-0348-7442-7_1. [DOI] [PubMed] [Google Scholar]
  18. Poole A. R., Rosenberg L. C., Reiner A., Ionescu M., Bogoch E., Roughley P. J. Contents and distributions of the proteoglycans decorin and biglycan in normal and osteoarthritic human articular cartilage. J Orthop Res. 1996 Sep;14(5):681–689. doi: 10.1002/jor.1100140502. [DOI] [PubMed] [Google Scholar]
  19. Rizkalla G., Reiner A., Bogoch E., Poole A. R. Studies of the articular cartilage proteoglycan aggrecan in health and osteoarthritis. Evidence for molecular heterogeneity and extensive molecular changes in disease. J Clin Invest. 1992 Dec;90(6):2268–2277. doi: 10.1172/JCI116113. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Serra R., Johnson M., Filvaroff E. H., LaBorde J., Sheehan D. M., Derynck R., Moses H. L. Expression of a truncated, kinase-defective TGF-beta type II receptor in mouse skeletal tissue promotes terminal chondrocyte differentiation and osteoarthritis. J Cell Biol. 1997 Oct 20;139(2):541–552. doi: 10.1083/jcb.139.2.541. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Song X. y., Zeng L., Jin W., Thompson J., Mizel D. E., Lei K., Billinghurst R. C., Poole A. R., Wahl S. M. Secretory leukocyte protease inhibitor suppresses the inflammation and joint damage of bacterial cell wall-induced arthritis. J Exp Med. 1999 Aug 16;190(4):535–542. doi: 10.1084/jem.190.4.535. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Stoop R., Buma P., van der Kraan P. M., Hollander A. P., Clark Billinghurst R., Robin Poole A., van den Berg W. B. Differences in type II collagen degradation between peripheral and central cartilage of rat stifle joints after cranial cruciate ligament transection. Arthritis Rheum. 2000 Sep;43(9):2121–2131. doi: 10.1002/1529-0131(200009)43:9<2121::AID-ANR24>3.0.CO;2-N. [DOI] [PubMed] [Google Scholar]
  23. Stoop R., van der Kraan P. M., Buma P., Hollander A. P., Billinghurst R. C., Poole A. R., van den Berg W. B. Type II collagen degradation in spontaneous osteoarthritis in C57Bl/6 and BALB/c mice. Arthritis Rheum. 1999 Nov;42(11):2381–2389. doi: 10.1002/1529-0131(199911)42:11<2381::AID-ANR17>3.0.CO;2-E. [DOI] [PubMed] [Google Scholar]
  24. Verzijl Nicole, DeGroot Jeroen, Ben Zaken Chaya, Brau-Benjamin Orit, Maroudas Alice, Bank Ruud A., Mizrahi Joe, Schalkwijk Casper G., Thorpe Suzanne R., Baynes John W. Crosslinking by advanced glycation end products increases the stiffness of the collagen network in human articular cartilage: a possible mechanism through which age is a risk factor for osteoarthritis. Arthritis Rheum. 2002 Jan;46(1):114–123. doi: 10.1002/1529-0131(200201)46:1<114::AID-ART10025>3.0.CO;2-P. [DOI] [PubMed] [Google Scholar]
  25. Wu C. William, Tchetina Elena V., Mwale Fackson, Hasty Karen, Pidoux Isabelle, Reiner Agnes, Chen Jeffrey, Van Wart Harold E., Poole A. Robin. Proteolysis involving matrix metalloproteinase 13 (collagenase-3) is required for chondrocyte differentiation that is associated with matrix mineralization. J Bone Miner Res. 2002 Apr;17(4):639–651. doi: 10.1359/jbmr.2002.17.4.639. [DOI] [PubMed] [Google Scholar]
  26. Wu William, Billinghurst R. Clark, Pidoux Isabelle, Antoniou John, Zukor David, Tanzer Michael, Poole A. Robin. Sites of collagenase cleavage and denaturation of type II collagen in aging and osteoarthritic articular cartilage and their relationship to the distribution of matrix metalloproteinase 1 and matrix metalloproteinase 13. Arthritis Rheum. 2002 Aug;46(8):2087–2094. doi: 10.1002/art.10428. [DOI] [PubMed] [Google Scholar]
  27. Yang X., Chen L., Xu X., Li C., Huang C., Deng C. X. TGF-beta/Smad3 signals repress chondrocyte hypertrophic differentiation and are required for maintaining articular cartilage. J Cell Biol. 2001 Apr 2;153(1):35–46. doi: 10.1083/jcb.153.1.35. [DOI] [PMC free article] [PubMed] [Google Scholar]

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