Transcriptional regulation of collagenase (MMP-1, MMP-13) genes in arthritis: integration of complex signaling pathways for the recruitment of gene-specific transcription factors.
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-alpha, 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.
Vincenti
Matthew P
MP
Department of Medicine, Dartmouth Medical School, Hanover, New Hampshire 03755, USA. mpv@dartmouth.edu
Brinckerhoff
Constance E
CE
D000818:Animals; D001172:Arthritis, Rheumatoid / Q000201:enzymology* / Q000235:genetics; D017364:Collagenases / Q000235:genetics*; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D020781:Matrix Metalloproteinase 1 / Q000235:genetics*; D053509:Matrix Metalloproteinase 13; D020929:Mitogen-Activated Protein Kinase Kinases / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D010003:Osteoarthritis / Q000201:enzymology* / Q000235:genetics; D015398:Signal Transduction; D014157:Transcription Factors / Q000502:physiology*
D016328:NF-kappa B; D014157:Transcription Factors; D020929:Mitogen-Activated Protein Kinase Kinases; D017364:Collagenases; C507079:MMP13 protein, human; D053509:Matrix Metalloproteinase 13; D020781:Matrix Metalloproteinase 1