PTEN Reduces BMP9-Induced Osteogenic Differentiation Through Inhibiting Wnt10b in Mesenchymal Stem Cells
Bone morphogenetic protein 9 (BMP9) is one of the most efficacious osteogenic cytokines. PTEN and Wnt10b are both implicated in regulating the osteogenic potential of BMP9, but the potential relationship between them is unknown. In this study, we determined whether PTEN could reduce the expression o...
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2021-02-01
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doaj-437f2c67472042bcb4bddfb0f1e292942021-02-04T05:29:28ZengFrontiers Media S.A.Frontiers in Cell and Developmental Biology2296-634X2021-02-01810.3389/fcell.2020.608544608544PTEN Reduces BMP9-Induced Osteogenic Differentiation Through Inhibiting Wnt10b in Mesenchymal Stem CellsFu-Shu Li0Fu-Shu Li1Pei-Pei Li2Pei-Pei Li3Ling Li4Ling Li5Yan Deng6Yan Deng7Ying Hu8Ying Hu9Bai-Cheng He10Bai-Cheng He11Department of Pharmacology, School of Pharmacy, Chongqing Medical University, Chongqing, ChinaKey Laboratory of Biochemistry and Molecular Pharmacology of Chongqing, Chongqing Medical University, Chongqing, ChinaDepartment of Pharmacology, School of Pharmacy, Chongqing Medical University, Chongqing, ChinaKey Laboratory of Biochemistry and Molecular Pharmacology of Chongqing, Chongqing Medical University, Chongqing, ChinaDepartment of Pharmacology, School of Pharmacy, Chongqing Medical University, Chongqing, ChinaKey Laboratory of Biochemistry and Molecular Pharmacology of Chongqing, Chongqing Medical University, Chongqing, ChinaDepartment of Pharmacology, School of Pharmacy, Chongqing Medical University, Chongqing, ChinaKey Laboratory of Biochemistry and Molecular Pharmacology of Chongqing, Chongqing Medical University, Chongqing, ChinaDepartment of Pharmacology, School of Pharmacy, Chongqing Medical University, Chongqing, ChinaKey Laboratory of Biochemistry and Molecular Pharmacology of Chongqing, Chongqing Medical University, Chongqing, ChinaDepartment of Pharmacology, School of Pharmacy, Chongqing Medical University, Chongqing, ChinaKey Laboratory of Biochemistry and Molecular Pharmacology of Chongqing, Chongqing Medical University, Chongqing, ChinaBone morphogenetic protein 9 (BMP9) is one of the most efficacious osteogenic cytokines. PTEN and Wnt10b are both implicated in regulating the osteogenic potential of BMP9, but the potential relationship between them is unknown. In this study, we determined whether PTEN could reduce the expression of Wnt10b during the osteogenic process initialized by BMP9 in mesenchymal stem cells (MSCs) and the possible molecular mechanism. We find that PTEN is inhibited by BMP9 in MSCs, but Wnt10b is increased simultaneously. The BMP9-induced osteogenic markers are reduced by PTEN but increased by silencing PTEN. The effects of knockdown PTEN on elevating BMP9-induced osteogenic markers are almost abolished by knockdown of Wnt10b. On the contrary, the BMP9-increased ALP activities and mineralization are both inhibited by PTEN but almost reversed by the combination of Wnt10b. Bone masses induced by BMP9 are enhanced by knockdown of PTEN, which is reduced by knockdown of Wnt10b. The BMP9-increased Wnt10b is decreased by PTEN but enhanced by knockdown of PTEN. Meanwhile, the BMP9-induced Wnt10b is also reduced by a PI3K-specific inhibitor (Ly294002) or rapamycin, respectively. The BMP9-induced phosphorylation of CREB or Smad1/5/9 is also reduced by PTEN, but enhanced by PTEN knockdown. In addition, p-CREB interacts with p-Smad1/5/9 in MSCs, and p-CREB or p-Smad1/5/9 are both enriched at the promoter region of Wnt10b. Our findings indicate that inhibitory effects of PTEN on BMP9's osteogenic potential may be partially mediated through decreasing the expression of Wnt10b via the disturbance of interaction between CREB and BMP/Smad signaling.https://www.frontiersin.org/articles/10.3389/fcell.2020.608544/fullphosphatase and tensin homolog deleted on chromosome 10WNT10BBMP9osteogenic differentiationmesenchymal stem cell |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Fu-Shu Li Fu-Shu Li Pei-Pei Li Pei-Pei Li Ling Li Ling Li Yan Deng Yan Deng Ying Hu Ying Hu Bai-Cheng He Bai-Cheng He |
spellingShingle |
Fu-Shu Li Fu-Shu Li Pei-Pei Li Pei-Pei Li Ling Li Ling Li Yan Deng Yan Deng Ying Hu Ying Hu Bai-Cheng He Bai-Cheng He PTEN Reduces BMP9-Induced Osteogenic Differentiation Through Inhibiting Wnt10b in Mesenchymal Stem Cells Frontiers in Cell and Developmental Biology phosphatase and tensin homolog deleted on chromosome 10 WNT10B BMP9 osteogenic differentiation mesenchymal stem cell |
author_facet |
Fu-Shu Li Fu-Shu Li Pei-Pei Li Pei-Pei Li Ling Li Ling Li Yan Deng Yan Deng Ying Hu Ying Hu Bai-Cheng He Bai-Cheng He |
author_sort |
Fu-Shu Li |
title |
PTEN Reduces BMP9-Induced Osteogenic Differentiation Through Inhibiting Wnt10b in Mesenchymal Stem Cells |
title_short |
PTEN Reduces BMP9-Induced Osteogenic Differentiation Through Inhibiting Wnt10b in Mesenchymal Stem Cells |
title_full |
PTEN Reduces BMP9-Induced Osteogenic Differentiation Through Inhibiting Wnt10b in Mesenchymal Stem Cells |
title_fullStr |
PTEN Reduces BMP9-Induced Osteogenic Differentiation Through Inhibiting Wnt10b in Mesenchymal Stem Cells |
title_full_unstemmed |
PTEN Reduces BMP9-Induced Osteogenic Differentiation Through Inhibiting Wnt10b in Mesenchymal Stem Cells |
title_sort |
pten reduces bmp9-induced osteogenic differentiation through inhibiting wnt10b in mesenchymal stem cells |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Cell and Developmental Biology |
issn |
2296-634X |
publishDate |
2021-02-01 |
description |
Bone morphogenetic protein 9 (BMP9) is one of the most efficacious osteogenic cytokines. PTEN and Wnt10b are both implicated in regulating the osteogenic potential of BMP9, but the potential relationship between them is unknown. In this study, we determined whether PTEN could reduce the expression of Wnt10b during the osteogenic process initialized by BMP9 in mesenchymal stem cells (MSCs) and the possible molecular mechanism. We find that PTEN is inhibited by BMP9 in MSCs, but Wnt10b is increased simultaneously. The BMP9-induced osteogenic markers are reduced by PTEN but increased by silencing PTEN. The effects of knockdown PTEN on elevating BMP9-induced osteogenic markers are almost abolished by knockdown of Wnt10b. On the contrary, the BMP9-increased ALP activities and mineralization are both inhibited by PTEN but almost reversed by the combination of Wnt10b. Bone masses induced by BMP9 are enhanced by knockdown of PTEN, which is reduced by knockdown of Wnt10b. The BMP9-increased Wnt10b is decreased by PTEN but enhanced by knockdown of PTEN. Meanwhile, the BMP9-induced Wnt10b is also reduced by a PI3K-specific inhibitor (Ly294002) or rapamycin, respectively. The BMP9-induced phosphorylation of CREB or Smad1/5/9 is also reduced by PTEN, but enhanced by PTEN knockdown. In addition, p-CREB interacts with p-Smad1/5/9 in MSCs, and p-CREB or p-Smad1/5/9 are both enriched at the promoter region of Wnt10b. Our findings indicate that inhibitory effects of PTEN on BMP9's osteogenic potential may be partially mediated through decreasing the expression of Wnt10b via the disturbance of interaction between CREB and BMP/Smad signaling. |
topic |
phosphatase and tensin homolog deleted on chromosome 10 WNT10B BMP9 osteogenic differentiation mesenchymal stem cell |
url |
https://www.frontiersin.org/articles/10.3389/fcell.2020.608544/full |
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