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The effect of PPAR-γ inhibition on gene expression and the progression of induced osteogenic differentiation of human mesenchymal stem cells.

Journal article
Authors Cecilia Granéli
Camilla Karlsson
Helena Brisby
Anders Lindahl
Peter Thomsen
Published in Connective tissue research
Volume 55
Issue 4
Pages 262-274
ISSN 1607-8438
Publication year 2014
Published at Institute of Biomedicine
Institute of Clinical Sciences, Department of Biomaterials
Institute of Clinical Sciences, Department of Orthopaedics
Pages 262-274
Language en
Subject categories Orthopedics


Abstract Mesenchymal stem cells (MSCs) can differentiate into several cell types, such as osteoblasts and adipocytes, both in vitro and in vivo. Although these two differentiation pathways are distinct from each other, cross-communication between cells of the two lineages exists both systemically and peripherally in the tissue. The transcription factor PPAR-γ, the main switch in adipogenic differentiation of MSCs, has previously been described to have a negative effect on osteogenic differentiation. The aim of this study was to investigate the effect of PPAR-γ inhibition on osteogenic differentiation of human MSCs, in vitro. ECM analysis and quantification of osteogenic markers, revealed how these cells respond when the adipogenic differentiation pathway is blocked during induction of osteogenic differentiation. The inhibition leads to a significant increase in mineralization of the extracellular matrix, as well as an increased activity or up-regulated gene expression of ALP, the key enzyme involved in matrix mineralization. Furthermore, it was also demonstrated by microarray analysis, that PPAR-γ inhibition during osteogenic induction leads to a significant up-regulation of a number of genes related to both osteogenesis and adipogenesis such as c10orf10, leptin, GDF5, and KLF15. In conclusion, inhibition of PPAR-γ during induction of osteogenesis leads to increased osteogenic differentiation of human MSCs.

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