Icariin stimulates differentiation of bone marrow-derived mesenchymal stem cells (BM-MSCs) through activation of cAMP/PKA/CREB

Detalhes bibliográficos
Autor(a) principal: Lou, Dan
Data de Publicação: 2019
Outros Autores: Ye, Jifeng, Yang, Lianhua, Wu, Zheng, Zheng, Wei, Zhang, Hui
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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spelling 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
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