Expression of the ectodomain-releasing protease ADAM17 is directly regulated by the osteosarcoma and bone-related transcription factor RUNX2

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dc.contributor.authorAraya, Héctor F.
dc.contributor.authorSepúlveda, Hugo
dc.contributor.authorLizama, Carlos O.
dc.contributor.authorVega, Oscar A.
dc.contributor.authorJerez, Sofía
dc.contributor.authorBriceño, Pedro F.
dc.contributor.authorThaler, Romane
dc.contributor.authorRiester, Scott M.
dc.contributor.authorAntonelli, Marcelo
dc.contributor.authorSalazar-Onfray, Flavio
dc.contributor.authorRodríguez, Juan Pablo
dc.contributor.authorMoreno, Ricardo D.
dc.contributor.authorMontecino, Martín
dc.contributor.authorCharbonneau, Martín
dc.contributor.authorDubois, Claire M.
dc.contributor.authorStein, Gary S.
dc.contributor.authorvan Wijnen, Andre J.
dc.contributor.authorGalindo, Mario A.
dc.date.accessioned2022-07-01T00:17:54Z
dc.date.available2022-07-01T00:17:54Z
dc.date.issued2018-11
dc.descriptionIndexación Scopuses
dc.description.abstractOsteoblast differentiation is controlled by transcription factor RUNX2 which temporally activates or represses several bone-related genes, including those encoding extracellular matrix proteins or factors that control cell-cell, and cell-matrix interactions. Cell-cell communication in the many skeletal pericellular micro-niches is critical for bone development and involves paracrine secretion of growth factors and morphogens. This paracrine signaling is in part regulated by “A Disintegrin And Metalloproteinase” (ADAM) proteins. These cell membrane-associated metalloproteinases support proteolytic release (“shedding”) of protein ectodomains residing at the cell surface. We analyzed microarray and RNA-sequencing data for Adam genes and show that Adam17, Adam10, and Adam9 are stimulated during BMP2 mediated induction of osteogenic differentiation and are robustly expressed in human osteoblastic cells. ADAM17, which was initially identified as a tumor necrosis factor alpha (TNFα) converting enzyme also called (TACE), regulates TNFα-signaling pathway, which inhibits osteoblast differentiation. We demonstrate that Adam17 expression is suppressed by RUNX2 during osteoblast differentiation through the proximal Adam17 promoter region (−0.4 kb) containing two functional RUNX2 binding motifs. Adam17 downregulation during osteoblast differentiation is paralleled by increased RUNX2 expression, cytoplasmic-nuclear translocation and enhanced binding to the Adam17 proximal promoter. Forced expression of Adam17 reduces Runx2 and Alpl expression, indicating that Adam17 may negatively modulate osteoblast differentiation. These findings suggest a novel regulatory mechanism involving a reciprocal Runx2-Adam17 negative feedback loop to regulate progression through osteoblast differentiation. Our results suggest that RUNX2 may control paracrine signaling through regulation of ectodomain shedding at the cell surface of osteoblasts by directly suppressing Adam17 expression. © 2018 Wiley Periodicals, Inc.es
dc.description.urihttps://onlinelibrary-wiley-com.recursosbiblioteca.unab.cl/doi/epdf/10.1002/jcb.26832
dc.identifier.citationJournal of Cellular Biochemistry Volume 119, Issue 10, Pages 8204 - 8219November 2018es
dc.identifier.doihttps://onlinelibrary-wiley-com.recursosbiblioteca.unab.cl/doi/epdf/10.1002/jcb.26832
dc.identifier.issn07302312
dc.identifier.urihttps://repositorio.unab.cl/xmlui/handle/ria/23107
dc.language.isoenes
dc.publisherWiley-Liss Inc.es
dc.subjectCleidocranial Dysplasiaes
dc.subjectOsteoblastses
dc.subjectTranscription Factor RUNX2es
dc.titleExpression of the ectodomain-releasing protease ADAM17 is directly regulated by the osteosarcoma and bone-related transcription factor RUNX2es
dc.typeArtículoes
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