Glycogen synthase kinase 3β promotes osteogenic differentiation of murine adipose-derived stromal cells.
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,...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2013-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3546989?pdf=render |
| _version_ | 1818201653067644928 |
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| author | Jeong-Eun Huh Ryeojin Ko Hyun Ju Jung Soo Young Lee |
| author_facet | Jeong-Eun Huh Ryeojin Ko Hyun Ju Jung Soo Young Lee |
| author_sort | Jeong-Eun Huh |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-12T02:56:58Z |
| format | Article |
| id | doaj.art-bce2f90296b3482bbc2d473a7558011d |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-12T02:56:58Z |
| publishDate | 2013-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-bce2f90296b3482bbc2d473a7558011d2022-12-22T00:40:43ZengPublic Library of Science (PLoS)PLoS ONE1932-62032013-01-0181e5455110.1371/journal.pone.0054551Glycogen synthase kinase 3β promotes osteogenic differentiation of murine adipose-derived stromal cells.Jeong-Eun HuhRyeojin KoHyun Ju JungSoo Young LeeAlthough 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.http://europepmc.org/articles/PMC3546989?pdf=render |
| spellingShingle | Jeong-Eun Huh Ryeojin Ko Hyun Ju Jung Soo Young Lee Glycogen synthase kinase 3β promotes osteogenic differentiation of murine adipose-derived stromal cells. PLoS ONE |
| title | Glycogen synthase kinase 3β promotes osteogenic differentiation of murine adipose-derived stromal cells. |
| title_full | Glycogen synthase kinase 3β promotes osteogenic differentiation of murine adipose-derived stromal cells. |
| title_fullStr | Glycogen synthase kinase 3β promotes osteogenic differentiation of murine adipose-derived stromal cells. |
| title_full_unstemmed | Glycogen synthase kinase 3β promotes osteogenic differentiation of murine adipose-derived stromal cells. |
| title_short | Glycogen synthase kinase 3β promotes osteogenic differentiation of murine adipose-derived stromal cells. |
| title_sort | glycogen synthase kinase 3β promotes osteogenic differentiation of murine adipose derived stromal cells |
| url | http://europepmc.org/articles/PMC3546989?pdf=render |
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