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Aggrecan heterogeneity in articular cartilage from patients with osteoarthritis

Authors
  • Mort, John S.1, 2
  • Geng, Yeqing1
  • Fisher, William D.2, 3
  • Roughley, Peter J.1, 2
  • 1 Research Unit, Shriners Hospital for Children, 1003, boul. Décarie, Montreal, Quebec, H4A 0A9, Canada , Montreal (Canada)
  • 2 McGill University, Department of Surgery, Montreal, Quebec, Canada , Montreal (Canada)
  • 3 McGill University Health Center, Division of Orthopaedics, 1650 Cedar Avenue, Montreal, Quebec, H3G 1A4, Canada , Montreal (Canada)
Type
Published Article
Journal
BMC Musculoskeletal Disorders
Publisher
Springer (Biomed Central Ltd.)
Publication Date
Feb 18, 2016
Volume
17
Issue
1
Identifiers
DOI: 10.1186/s12891-016-0944-8
Source
Springer Nature
Keywords
License
Green

Abstract

BackgroundAggrecan degradation is the hallmark of cartilage degeneration in osteoarthritis (OA), though it is unclear whether a common proteolytic process occurs in all individuals.MethodsAggrecan degradation in articular cartilage from the knees of 33 individuals with OA, who were undergoing joint replacement surgery, was studied by immunoblotting of tissue extracts.ResultsMatrix metalloproteinases (MMPs) and aggrecanases are the major proteases involved in aggrecan degradation within the cartilage, though the proportion of aggrecan cleavage attributable to MMPs or aggrecanases was variable between individuals. However, aggrecanases were more associated with the increase in aggrecan loss associated with OA than MMPs. While the extent of aggrecan cleavage was highly variable between individuals, it was greatest in areas of cartilage adjacent to sites of cartilage erosion compared to sites more remote within the same joint. Analysis of link protein shows that in some individuals additional proteolytic mechanisms must also be involved to some extent.ConclusionsThe present studies indicate that there is no one protease, or a fixed combination of proteases, responsible for cartilage degradation in OA. Thus, rather than targeting the individual proteases for OA therapy, directing research to techniques that control global protease generation may be more productive.

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