Characterization of opticin digestion by proteases involved in osteoarthritis development

Laura Tío, Johanne Martel-Pelletier, Jean Pierre Pelletier, Paul N. Bishop, Peter Roughley, Aina Farran, Pere Benito, Jordi Monfort

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8 Citations (Scopus)

Abstract

Objective: Opticin is a class III member of the small leucine-rich repeat proteoglycan (SLRP) family, produced in articular joint tissues. In normal and osteoarthritic (OA) cartilage, opticin is degraded. This study aimed to assess whether human cartilage opticin is degraded by the main proteases involved in OA pathophysiology, and to determine the protease cleavage sites of this SLRP. Methods: We analyzed the proteolytic activity of matrix metalloproteinases (MMPs)-1, -2, -3, -7, -8 and -9, and ADAMTS-4 and -5 on proteoglycan extracts from normal and moderately fibrillated OA human cartilage, and on recombinant human opticin. Opticin degradation was analyzed by Western blotting and cleavage sites were determined by sequence analysis. Results: All eight proteases digested opticin from proteoglycan extracts from both normal and OA samples, as well as recombinant human opticin, MMP-2 and MMP-7 are the proteases that degrade recombinant human opticin most efficiently. The opticin cleavage site determined for these MMPs was between the glycosylation and leucine-rich repeat domains. MMP-7 had two additional digestion sites near the N-terminal end of opticin. Conclusion: Opticin is a substrate for several MMPs and aggrecanases involved during OA cartilage degradation, and seems to be a preferential substrate for MMP-7. The role of opticin in cartilage degeneration could be related to decreased levels of intact opticin, followed by its proteolytic degradation, which in turn may stimulate some of the modifications observed in the OA cartilage, such as neovascularisation and changes in the extracellular matrix. © 2013 Société française de rhumatologie.
Original languageEnglish
Pages (from-to)137-141
JournalJoint Bone Spine
Volume81
Issue number2
DOIs
Publication statusPublished - 1 Jan 2014

Keywords

  • Aggrecanases
  • Metalloproteases
  • Opticin
  • Osteoarthritis
  • Small leucine-rich repeat proteoglycans

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