Authors: Silvia Smaldone Luca Carta Francesco Ramirez
Publish Date: 2011/05/03
Volume: 344, Issue: 3, Pages: 511-
Abstract
Fibrillin1 and fibrillin2 are structural components of the extracellular matrix which are also involved in modulating local TGFβ and BMP bioavailability Loss of fibrillin1 or fibrillin2 is associated with perturbed osteoblast maturation principally as the result of unbalanced TGFβ and BMP signaling Here we demonstrated that stable expression of small hairpin RNAs against fibrillin1Fbn1 or fibrillin2 Fbn2 transcripts in the clonal osteoprogenitor cell line KusaA1 led to the same phenotypic and molecular manifestations as germline Fbn1 or Fbn2null mutations in primary calvarial osteoblast cultures Proofofconcept experiments are also presented showing that Fbn1 or Fbn2silenced KusaA1 cell lines are suitable models to identify candidate determinants of osteogenesis which are under the control of extracellular microfibrils Specific findings included the inference of a potential role for fibrillin1mediated cell–matrix interactions in regulating KusaA1 proliferation the possibility of fibrillin2 involvement in modulating the activity of transcription factor Runx2 by restricting microRNA expression and/or processing and the suggestion that fibrillin1 and fibrillin2 influence Notch signaling indirectly by differentially regulating BMP signaling Collectively the data reiterated the notion that fibrillin1 and fibrillin2 exert opposite effects on osteoblast differentiation through the discrete modulation of a broad network of interacting signaling molecules
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