A Comparative Study of Fibronectin Cleavage by MMP-1, -3, -13, and -14

Xiaorong Zhang, Christopher T. Chen, Madhu Bhargava, Peter A. Torzilli

Research output: Contribution to journalArticle

18 Scopus citations

Abstract

Fibronectin fragments are important for synovial inflammation and the progression of arthritis, and thus, identifying potential enzymatic pathways that generate these fragments is of vital importance. The objective of this study was to determine the cleavage efficiency of fibronectin by matrix metalloproteinases (MMP-1, MMP-3, MMP-13, and MMP-14). Intact human plasma fibronectin was co-incubated with activated MMPs in neutral or acidic pH for up to 24 hours at 37 °C. The size and distribution of fibronectin fragments were determined by Western blot analysis using antibodies that recognized the N-terminals of fibronectin. All MMPs were able to cleave fibronectin at neutral pH. MMP-13 and -14 had the highest efficiency followed by MMP-3 and -1. MMP-3, -13, and -14 generated 70-kDa fragments, a known pro-inflammatory peptide. Further degradation of fibronectin fragments was only found for MMP-13 and -14, generating 52-kDa, 40-kDa, 32-kDa, and 29-kDa fragments. Fibronectin fragments of similar size were also found in the articular cartilage of femoral condyles of normal bovine knee joints. At acidic pH (5.5), the activities of MMP-1 and -14 were nearly abolished, while MMP-3 had a greater efficiency than MMP-13 even though the activities of both MMPs were significantly reduced. These findings suggest that MMP-13 and -14 may play a significant role in the cleavage of fibronectin and the production of fibronectin fragments in normal and arthritic joints.

Original languageEnglish (US)
Pages (from-to)267-277
Number of pages11
JournalCartilage
Volume3
Issue number3
DOIs
StatePublished - Jul 1 2012

Keywords

  • cartilage
  • fibronectin
  • fibronectin fragments
  • matrix metalloproteinases

ASJC Scopus subject areas

  • Immunology and Allergy
  • Biomedical Engineering
  • Physical Therapy, Sports Therapy and Rehabilitation

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