Journal
ARTHRITIS RESEARCH & THERAPY
Volume 5, Issue 2, Pages 94-103Publisher
BMC
DOI: 10.1186/ar630
Keywords
ADAMTS; chondrocytes; matrix metalloproteinases; osteoarthritis
Categories
Funding
- NATIONAL INSTITUTE OF ARTHRITIS AND MUSCULOSKELETAL AND SKIN DISEASES [R01AR040994] Funding Source: NIH RePORTER
- NIAMS NIH HHS [R01 AR040994, AR40994] Funding Source: Medline
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The loss of extracellular matrix macromolecules from the cartilage results in serious impairment of joint function. Metalloproteinases called 'aggrecanases' that cleave the Glu(373)-Ala(374) bond of the aggrecan core protein play a key role in the early stages of cartilage destruction in rheumatoid arthritis and in osteoarthritis. Three members of the ADAMTS family of proteinases, ADAMTS-1, ADAMTS-4 and ADAMTS-5, have been identified as aggrecanases. Matrix metalloproteinases, which are also found in arthritic joints, cleave aggrecans, but at a distinct site from the aggrecanases (i.e. Asn(341)-Phe(342)). The present review discuss the enzymatic properties of the three known aggrecanases, the regulation of their activities, and their role in cartilage matrix breakdown during the development of arthritis in relation to the action of matrix metalloproteinases.
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