Transcriptional regulation of collagenase (MMP-1, MMP-13) genes in arthritis: integration of complex signaling pathways for the recruitment of gene-specific transcription factors

By Matthew P. Vincenti, C. Brinckerhoff. Arthritis Research & Therapy, 2001

826 citations recorded by the source corpus.

Matrix metalloproteinase (MMP)-1, MMP-8 and MMP-13 are interstitial collagenases that degrade type II collagen in cartilage; this is a committed step in the progression of rheumatoid arthritis and osteoarthritis. Of these enzymes, the expression of MMP-1 and MMP-13 is substantially increased in response to IL-1 and tumor necrosis factor-α, and elevated levels of these collagenases are observed in arthritic tissues. Therefore, cytokine-mediated MMP-1 and MMP-13 gene regulation is an important issue in arthritis research. In this review, we discuss current models of MMP-1 and MMP-13 transcriptional regulation, with a focus on signaling intermediates and transcription factors that may be future targets for the development of new arthritis drugs.

Subfields: Cancer Research, Rheumatology

View Paper: https://www.semanticscholar.org/paper/df681798522ff9248f9ec9edde204affe73c9b46

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Citations in the corpus

• NF-κB and the immune response (2006, background): “Finally, matrix metalloproteinases (MMPs) also are crucial mediators of local inflammation and leukocyte chemotaxis; and their expression is also regulated by NF-kB (Vincenti et al., 1998; Vincenti and Brinckerhoff, 2002; Lai et al., 2003).”
• The Role of Inflammatory and Anti-Inflammatory Cytokines in the Pathogenesis of Osteoarthritis (2014, background): “In addition to the decrease in the synthesis of the building blocks, the IL-1β affects the operation of chondrocytes in the synthesis of enzymes from the group ofmetalloproteinases (MMPs),mainly interstitial collagenase (MMP-1), stromelysin-1 (MMP-3), and collagenase 3 (MMP13), which have a destruct”
• Myocardial matrix remodeling and the matrix metalloproteinases: influence on cardiac form and function. (2007, background): “Indeed, exposure of ANG II in cell culture systems causes a concordant induction of transcription factors that would bind to MMP promoter regions and increased MMP levels (22, 45, 180, 471, 480).”
• Physiology and pathophysiology of matrix metalloproteases (2010, background): “Since MMP-1 appears to play a key role in the turnover of ECM, deregulation of MMP-1 activity has been hypothesized to be involved in various diseases related to excessive or insufficient ECM turnover, such as arthritis (Vincenti et al. 1994; Vincenti and Brinckerhoff 2002), cancer (Benbow et al.”
• Regulation of matrix metalloproteinase gene expression (2007, background): “The NF-kB pathway also contributes to the regulation of MMP-1, -3, and -11 expression (Vincenti and Brinckerhoff, 2002), although this is somewhat unexpected, considering the absence of a functional NF-kB-binding site within the promoters of these genes.”