Icariin stimulates differentiation of bone marrow-derived mesenchymal stem cells (BM-MSCs) through activation of cAMP/PKA/CREB
Autor(a) principal: | |
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Data de Publicação: | 2019 |
Outros Autores: | , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Brazilian Journal of Pharmaceutical Sciences |
Texto Completo: | https://www.revistas.usp.br/bjps/article/view/180962 |
Resumo: | Icariin, a prenylated flavonol glycoside isolated from Epimedium, has been considered as a potential alternative therapy for osteoporosis. The present study aimed to clarify the detailed molecular mechanisms of action of icariin on osteoblast function, using bone marrow-derived mesenchymal stem cells (BM‑MSCs). BM-MSCs were first stimulated by icariin. Then, gene and protein expression of cAMP/ PKA/CREB signaling molecules were analyzed by RT-PCR and western blotting (WB), and alkaline phosphatase (ALP) was analyzed in cell lysates by ELISA. MTT assays indicated that icariin did not have significant effects on cell viability up to 1 μM. Icariin showed a dose-dependent effect on the alkaline phosphatase activity of BM-MSCs. WB analysis showed that icariin treatment of BM-MSCs significantly enhanced the protein expression of protein kinase A (PKA) and cAMP-responsive element binding protein (CREB), while RT-PCR results showed that icariin dose-dependently increased the mRNA levels of PKA and CREB. Icariin induced BM-MSC differentiation by BMP2, Smad1, and Runx2. RT‑PCR and WB results indicated that icariin significantly increased the expression of BMP2, Smad1, and Runx2 in BM‑MSCs. These results suggest that icariin is an agonist of the cAMP/PKA/CREB pathway in BM-MSC differentiation, raising the possibility that it could be used in the treatment of osteoporosis. |
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oai:revistas.usp.br:article/180962 |
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Brazilian Journal of Pharmaceutical Sciences |
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Icariin stimulates differentiation of bone marrow-derived mesenchymal stem cells (BM-MSCs) through activation of cAMP/PKA/CREBIcariin/molecular mechanismsBM-MSCscAMPPKACREBIcariin, a prenylated flavonol glycoside isolated from Epimedium, has been considered as a potential alternative therapy for osteoporosis. The present study aimed to clarify the detailed molecular mechanisms of action of icariin on osteoblast function, using bone marrow-derived mesenchymal stem cells (BM‑MSCs). BM-MSCs were first stimulated by icariin. Then, gene and protein expression of cAMP/ PKA/CREB signaling molecules were analyzed by RT-PCR and western blotting (WB), and alkaline phosphatase (ALP) was analyzed in cell lysates by ELISA. MTT assays indicated that icariin did not have significant effects on cell viability up to 1 μM. Icariin showed a dose-dependent effect on the alkaline phosphatase activity of BM-MSCs. WB analysis showed that icariin treatment of BM-MSCs significantly enhanced the protein expression of protein kinase A (PKA) and cAMP-responsive element binding protein (CREB), while RT-PCR results showed that icariin dose-dependently increased the mRNA levels of PKA and CREB. Icariin induced BM-MSC differentiation by BMP2, Smad1, and Runx2. RT‑PCR and WB results indicated that icariin significantly increased the expression of BMP2, Smad1, and Runx2 in BM‑MSCs. These results suggest that icariin is an agonist of the cAMP/PKA/CREB pathway in BM-MSC differentiation, raising the possibility that it could be used in the treatment of osteoporosis.Universidade de São Paulo. Faculdade de Ciências Farmacêuticas2019-12-09info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfhttps://www.revistas.usp.br/bjps/article/view/18096210.1590/s2175-97902019000218300Brazilian Journal of Pharmaceutical Sciences; Vol. 55 (2019); e18300Brazilian Journal of Pharmaceutical Sciences; v. 55 (2019); e18300Brazilian Journal of Pharmaceutical Sciences; Vol. 55 (2019); e183002175-97901984-8250reponame:Brazilian Journal of Pharmaceutical Sciencesinstname:Universidade de São Paulo (USP)instacron:USPenghttps://www.revistas.usp.br/bjps/article/view/180962/167982Copyright (c) 2019 Brazilian Journal of Pharmaceutical Scienceshttp://creativecommons.org/licenses/by/4.0info:eu-repo/semantics/openAccessLou, Dan Ye, Jifeng Yang, Lianhua Wu, Zheng Zheng, Wei Zhang, Hui 2021-01-19T16:47:29Zoai:revistas.usp.br:article/180962Revistahttps://www.revistas.usp.br/bjps/indexPUBhttps://old.scielo.br/oai/scielo-oai.phpbjps@usp.br||elizabeth.igne@gmail.com2175-97901984-8250opendoar:2021-01-19T16:47:29Brazilian Journal of Pharmaceutical Sciences - Universidade de São Paulo (USP)false |
dc.title.none.fl_str_mv |
Icariin stimulates differentiation of bone marrow-derived mesenchymal stem cells (BM-MSCs) through activation of cAMP/PKA/CREB |
title |
Icariin stimulates differentiation of bone marrow-derived mesenchymal stem cells (BM-MSCs) through activation of cAMP/PKA/CREB |
spellingShingle |
Icariin stimulates differentiation of bone marrow-derived mesenchymal stem cells (BM-MSCs) through activation of cAMP/PKA/CREB Lou, Dan Icariin/molecular mechanisms BM-MSCs cAMP PKA CREB |
title_short |
Icariin stimulates differentiation of bone marrow-derived mesenchymal stem cells (BM-MSCs) through activation of cAMP/PKA/CREB |
title_full |
Icariin stimulates differentiation of bone marrow-derived mesenchymal stem cells (BM-MSCs) through activation of cAMP/PKA/CREB |
title_fullStr |
Icariin stimulates differentiation of bone marrow-derived mesenchymal stem cells (BM-MSCs) through activation of cAMP/PKA/CREB |
title_full_unstemmed |
Icariin stimulates differentiation of bone marrow-derived mesenchymal stem cells (BM-MSCs) through activation of cAMP/PKA/CREB |
title_sort |
Icariin stimulates differentiation of bone marrow-derived mesenchymal stem cells (BM-MSCs) through activation of cAMP/PKA/CREB |
author |
Lou, Dan |
author_facet |
Lou, Dan Ye, Jifeng Yang, Lianhua Wu, Zheng Zheng, Wei Zhang, Hui |
author_role |
author |
author2 |
Ye, Jifeng Yang, Lianhua Wu, Zheng Zheng, Wei Zhang, Hui |
author2_role |
author author author author author |
dc.contributor.author.fl_str_mv |
Lou, Dan Ye, Jifeng Yang, Lianhua Wu, Zheng Zheng, Wei Zhang, Hui |
dc.subject.por.fl_str_mv |
Icariin/molecular mechanisms BM-MSCs cAMP PKA CREB |
topic |
Icariin/molecular mechanisms BM-MSCs cAMP PKA CREB |
description |
Icariin, a prenylated flavonol glycoside isolated from Epimedium, has been considered as a potential alternative therapy for osteoporosis. The present study aimed to clarify the detailed molecular mechanisms of action of icariin on osteoblast function, using bone marrow-derived mesenchymal stem cells (BM‑MSCs). BM-MSCs were first stimulated by icariin. Then, gene and protein expression of cAMP/ PKA/CREB signaling molecules were analyzed by RT-PCR and western blotting (WB), and alkaline phosphatase (ALP) was analyzed in cell lysates by ELISA. MTT assays indicated that icariin did not have significant effects on cell viability up to 1 μM. Icariin showed a dose-dependent effect on the alkaline phosphatase activity of BM-MSCs. WB analysis showed that icariin treatment of BM-MSCs significantly enhanced the protein expression of protein kinase A (PKA) and cAMP-responsive element binding protein (CREB), while RT-PCR results showed that icariin dose-dependently increased the mRNA levels of PKA and CREB. Icariin induced BM-MSC differentiation by BMP2, Smad1, and Runx2. RT‑PCR and WB results indicated that icariin significantly increased the expression of BMP2, Smad1, and Runx2 in BM‑MSCs. These results suggest that icariin is an agonist of the cAMP/PKA/CREB pathway in BM-MSC differentiation, raising the possibility that it could be used in the treatment of osteoporosis. |
publishDate |
2019 |
dc.date.none.fl_str_mv |
2019-12-09 |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
https://www.revistas.usp.br/bjps/article/view/180962 10.1590/s2175-97902019000218300 |
url |
https://www.revistas.usp.br/bjps/article/view/180962 |
identifier_str_mv |
10.1590/s2175-97902019000218300 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
https://www.revistas.usp.br/bjps/article/view/180962/167982 |
dc.rights.driver.fl_str_mv |
Copyright (c) 2019 Brazilian Journal of Pharmaceutical Sciences http://creativecommons.org/licenses/by/4.0 info:eu-repo/semantics/openAccess |
rights_invalid_str_mv |
Copyright (c) 2019 Brazilian Journal of Pharmaceutical Sciences http://creativecommons.org/licenses/by/4.0 |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
application/pdf |
dc.publisher.none.fl_str_mv |
Universidade de São Paulo. Faculdade de Ciências Farmacêuticas |
publisher.none.fl_str_mv |
Universidade de São Paulo. Faculdade de Ciências Farmacêuticas |
dc.source.none.fl_str_mv |
Brazilian Journal of Pharmaceutical Sciences; Vol. 55 (2019); e18300 Brazilian Journal of Pharmaceutical Sciences; v. 55 (2019); e18300 Brazilian Journal of Pharmaceutical Sciences; Vol. 55 (2019); e18300 2175-9790 1984-8250 reponame:Brazilian Journal of Pharmaceutical Sciences instname:Universidade de São Paulo (USP) instacron:USP |
instname_str |
Universidade de São Paulo (USP) |
instacron_str |
USP |
institution |
USP |
reponame_str |
Brazilian Journal of Pharmaceutical Sciences |
collection |
Brazilian Journal of Pharmaceutical Sciences |
repository.name.fl_str_mv |
Brazilian Journal of Pharmaceutical Sciences - Universidade de São Paulo (USP) |
repository.mail.fl_str_mv |
bjps@usp.br||elizabeth.igne@gmail.com |
_version_ |
1800222914569568256 |