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Cartilage pp 41-61 | Cite as

Proteoglycan and Collagen Degradation in Osteoarthritis

  • Stephanie J. Gauci
  • Heather Stanton
  • Christopher B. Little
  • Amanda J. Fosang
Chapter

Abstract

The gradual loss of articular cartilage from the surface of articulating joints is a feature of osteoarthritis. It is marked by degradation of the cartilage matrix, including the large aggregating proteoglycan aggrecan, the small leucine-rich proteoglycans known as SLRPs and the fibrillar type II collagen. Aggrecan provides the water-holding capacity of cartilage, while the collagen II scaffold provides elastic restraint, aided by a protective coat of small leucine-rich proteoglycans. Damaged aggrecan is readily replaced by synthesis of new aggrecan; however, type II collagen can resist only a limited amount of proteolysis before cartilage function is compromised. In this review the major enzyme families of cartilage-degrading enzymes, the matrix metalloproteinases (MMPs) and a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS) families, are discussed. We examine factors that regulate MMP and ADAMTS activity, with a focus on MMP-13, ADAMTS-4 and ADAMTS-5 as the major protagonists of cartilage degradation. We also compare the effects of blocking aggrecanolysis and collagenolysis separately, or together, on cartilage erosion in a mouse model of osteoarthritis. The role of degraded matrix fragments in regulating inflammation in osteoarthritis, via Toll-like receptor signalling, is also discussed.

Keywords

Cartilage Erosion Aggrecan Degradation Cartilage Function Aggrecanase Activity Hemopexin Domain 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Springer International Publishing Switzerland 2017

Authors and Affiliations

  • Stephanie J. Gauci
    • 1
  • Heather Stanton
    • 1
  • Christopher B. Little
    • 2
  • Amanda J. Fosang
    • 1
  1. 1.University of Melbourne Department of Paediatrics and Murdoch Childrens Research InstituteRoyal Children’s HospitalParkvilleAustralia
  2. 2.Raymond Purves Bone and Joint Research Laboratories, Kolling Institute, Institute of Bone and Joint Research, Sydney Medical School NorthernUniversity of SydneySt. LeonardsAustralia

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