Induction of human ADAMTS-2 gene expression by IL-1 alpha is mediated by a multiple crosstalk of MEK/JNK and PI3K pathways in osteoblast like cells

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dc.contributor.authorAlper, Meltem
dc.contributor.authorAydemir, A. Tugsen
dc.contributor.authorKoçkar, Feray
dc.date.accessioned13.07.201910:50:10
dc.date.accessioned2019-07-16T09:15:38Z
dc.date.available13.07.201910:50:10
dc.date.available2019-07-16T09:15:38Z
dc.date.issued2015
dc.departmentAksaray Teknik Bilimler Meslek Yüksekokulu
dc.description.abstractUp-regulation of ADAMTS genes with proinflammatory cytokines is important for some pathological conditions such as osteoarthritis (OA) that is a disease based on ECM degradation in cartilage. IL-1 alpha is a proinflammatory cytokine and important both to normal and pathophysiologic conditions in cartilage and bone. Effects of some proinflammatory cytokines such as TNF-alpha and IL-1 beta on the some members of ADAMTS family have been investigated in some chondrocyte tissues or cell lines. However the effect of the IL-1 alpha on the expression of ADAMTS-2 and ADAMTS-3 gene expression in osteoblast like cell lines, remains unclear. Therefore, the aim of this study is to investigate the effect of IL-1 alpha on ADAMTS-2 and ADAMTS-3 gene expression in osteoblast like cells, Saos-2 and MG-63. The present study, for the first time, demonstrated that IL-1 alpha increases ADAMTS-2 and ADAMTS-3 gene expressions in both Saos-2 and MG-63 cells. Having correlation to mRNA induction, the upregulation of ADAMTS-2,-3 protein levels by IL-1 alpha stimulation is also observed. The inhibition studies showed that this upregulation occurred at the level of transcription, and there was no effect of IL-1 alpha on ADAMTS-2 mRNA half-life in Saos-2 cells. Transactivation potential of IL-1 alpha on ADAMTS-2 promoter was investigated by transient transfection assay. Specifically, IL-1 alpha strongly increased -658/+112 and -530/+112 ADAMTS-2 promoter constructs. Further, we analyzed signaling pathways involved in ADAMTS-2 induction. Pathway inhibition studies revealed that this upregulation depends on the activation of MEK, JNK and PI3K pathways. These findings suggested that IL-1 alpha is a strong positive regulator of ADAMTS-2 and ADAMTS-3 expression. These findings would provide novel insight into the pathophysiology of OA. (C) 2015 Published by Elsevier B.V.
dc.description.sponsorshipScientific and Technological Research Council of Turkey (TUBITAK) [212T200]; Balikesir University Scientific Research Projects Unit (BAP) [2010/39]
dc.description.sponsorshipThis work was supported mainly by the Scientific and Technological Research Council of Turkey (TUBITAK) (212T200) and partially by the Balikesir University Scientific Research Projects Unit (BAP) (2010/39). Saos-2 cells were kindly provided by Dr. Kenneth Wann (Cardiff, School of Biosciences, Cardiff UK).
dc.identifier.doi10.1016/j.gene.2015.07.064
dc.identifier.endpage327en_US
dc.identifier.issn0378-1119
dc.identifier.issn1879-0038
dc.identifier.issue2en_US
dc.identifier.pmid26232334
dc.identifier.scopusqualityQ2
dc.identifier.startpage321en_US
dc.identifier.urihttps://doi.org/10.1016/j.gene.2015.07.064
dc.identifier.urihttps://hdl.handle.net/20.500.12451/4433
dc.identifier.volume573en_US
dc.identifier.wosWOS:000362305000018
dc.identifier.wosqualityN/A
dc.indekslendigikaynakWeb of Science
dc.indekslendigikaynakScopus
dc.indekslendigikaynakPubMed
dc.language.isoen
dc.publisherElsevier
dc.relation.ispartofGene
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanı
dc.rightsinfo:eu-repo/semantics/openAccess
dc.subjectADAMTS-2
dc.subjectADAMTS-3
dc.subjectIL-1 alpha
dc.subjectSaos-2
dc.subjectMG-63
dc.subjectMEK/JNK/PI3K
dc.titleInduction of human ADAMTS-2 gene expression by IL-1 alpha is mediated by a multiple crosstalk of MEK/JNK and PI3K pathways in osteoblast like cells
dc.typeArticle

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