Transactivation of the human adamts-2 gene promoter through proinflammatory cytokine tnf-alpha in osteoblast-like cells
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TNF-ais a proinflammatory cytokine produced by numerous celltypes, including macrophages, lymphocytes, fibroblasts and kerat-inocytes in response to inflammation, infection and other envi-ronmental stresses. TNF-ahas critical functions in inflammatorydisorders such as rheumatoid arthritis and osteoarthritis. Extra-cellular matrix (ECM) degradation is the main concern of theseconditions and an important component in morphogenesis,organogenesis, and tissue remodeling, as well as in wound healingand tissue repair. ADAMTS family has been implicated in osteo-blast and cartilage. As well as MMPs, ADAMTS protease familyhas the capacity to degrade the ECM. A member of this family,ADAMTS-2, processes the amino terminus of the type I, II, IIIand V procollagens, main component of the ECMIn the present study we explored effects of TNF-ato transcrip-tional activity of the human ADAMTS-2 gene promoter in osteo-blast like cells, Saos-2. Cells were transiently transfected withpreviously constructed ADAMTS-2 promoter fragments and thereporter gene activity in these cells that were either left untreatedor exposed to TNF-awas determined. TNF-adependent induc-tion in reporter gene activity was obtained with all ADAMTS-2promoter constructs. The main signalling pathways that wereinvolved in ADAMTS-2 induction were also determined.Keywords:ADAMTS-2, IL-a, Saos-2, Collagen.Acknowledgement:This work was supported mainly by theScientific and Technological Research Council of Turkey (TUBI-TAK) (212T200) and partially by the Balikesir University Scien-tific Research Projects Unit (BAP) (2010/39).