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Glycogen Synthase Kinase 3β Promotes Osteogenic Differentiation of Murine Adipose-Derived Stromal Cells

Title
Glycogen Synthase Kinase 3β Promotes Osteogenic Differentiation of Murine Adipose-Derived Stromal Cells
Authors
Huh J.-E.Ko R.Jung H.J.Lee S.Y.
Ewha Authors
이수영
SCOPUS Author ID
이수영scopus
Issue Date
2013
Journal Title
PLoS ONE
ISSN
1932-6203JCR Link
Citation
vol. 8, no. 1
Indexed
SCIE; SCOPUS WOS scopus
Abstract
Although the role of glycogen synthase kinase 3β (GSK3β) in osteogenic differentiation of bone marrow-derived mesenchymal stromal cells (BMSCs) is well-characterized as a negative regulator of β-catenin, its effect on osteogenesis of adipose-derived stromal cells (ADSCs) is poorly understood. Here, we show that GSK3β positively regulates osteogenic differentiation of murine ADSCs. Gain-of-function studies showed that GSK3β promotes in vitro osteogenesis of ADSCs. Regulation of GSK3β activity in ADSCs, either by small interfering RNA (siRNA)-mediated GSK3β silencing or by pharmacological inhibitors, blunted osteogenesis and the expression of osteogenic markers. Importantly, we demonstrated that transgenic mice, engineered to overexpress the constitutively active GSK3β (GSK3β-S9A) mutant, exhibited a marked increase in osteogenesis, whereas expression of the catalytically inactive GSK3β (GSK3β-K85A) in mice inhibits osteogenic differentiation. Molecular analyses showed that the enhanced osteoblast differentiation induced by GSK3β was mediated by downregulation of β-catenin. Remarkably, β-catenin silencing enhances osteogenesis and osteoblast marker gene expression such as alkaline phosphatase (ALP) and osterix. Taken together, these findings demonstrate a novel role for GSK3β in the regulation of osteogenic differentiation in ADSCs. © 2013 Huh et al.
DOI
10.1371/journal.pone.0054551
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자연과학대학 > 생명과학전공 > Journal papers
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