Icariin Promotes the Osteogenic Action of BMP2 by Activating the cAMP Signaling Pathway

Icariin (ICA) is the main active flavonoid glucoside from herbs of the genus <i>Epimedium</i>; in traditional Chinese medicine, these herbs have long been prescribed for the treatment of bone fractures and osteoporosis. Several studies have shown that treatment with ICA can increase oste...

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Main Authors: Meng Chen, Yazhou Cui, Hui Li, Jing Luan, Xiaoyan Zhou, Jinxiang Han
Format: Article
Language:English
Published: MDPI AG 2019-10-01
Series:Molecules
Subjects:
Online Access:https://www.mdpi.com/1420-3049/24/21/3875
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spelling doaj-044a51303ed04bdf9df165930a115b572020-11-24T21:11:03ZengMDPI AGMolecules1420-30492019-10-012421387510.3390/molecules24213875molecules24213875Icariin Promotes the Osteogenic Action of BMP2 by Activating the cAMP Signaling PathwayMeng Chen0Yazhou Cui1Hui Li2Jing Luan3Xiaoyan Zhou4Jinxiang Han5School of Traditional Chinese Medicine, Shandong University of Traditional Chinese Medicine, Jinan 250355, ChinaShandong Medicinal Biotechnology Center, Key Laboratory for Biotech-Drugs of the Ministry of Health, Jinan 250062, ChinaDepartment of Toxicology, Shandong Center for Disease Control and Prevention, Jinan 250014, ChinaShandong Medicinal Biotechnology Center, Key Laboratory for Biotech-Drugs of the Ministry of Health, Jinan 250062, ChinaShandong Medicinal Biotechnology Center, Key Laboratory for Biotech-Drugs of the Ministry of Health, Jinan 250062, ChinaShandong Medicinal Biotechnology Center, Key Laboratory for Biotech-Drugs of the Ministry of Health, Jinan 250062, ChinaIcariin (ICA) is the main active flavonoid glucoside from herbs of the genus <i>Epimedium</i>; in traditional Chinese medicine, these herbs have long been prescribed for the treatment of bone fractures and osteoporosis. Several studies have shown that treatment with ICA can increase osteogenic differentiation and reduce bone loss in vivo and in vitro. However, the definite signaling pathway of this osteogenic effect remains unclear. In this study, we selected bone morphogenetic protein 2 (BMP2)-induced osteoblastic differentiation of multipotent mesenchymal progenitor C2C12 cells as a model of osteoblast differentiation. We investigated the effects of ICA on C2C12 cells osteogenic differentiation and the underlying molecular mechanisms. We found that ICA could enhance BMP2-mediated osteoblastic differentiation of C2C12 cells in a dose-dependent manner. Treatment with ICA activated the cAMP/PKA/CREB signaling axis in a time-dependent manner. Blocking cAMP signaling using the PKA selective inhibitor H89 significantly inhibited the stimulatory effect of ICA on osteogenesis. Therefore, the osteoinductive potential and the low cost of ICA indicate that it is a promising alternative treatment or promoter for enhancing the therapeutic effects of BMP2.https://www.mdpi.com/1420-3049/24/21/3875icariin (ica)osteoblast differentiationbmp2camp/pka/creb
collection DOAJ
language English
format Article
sources DOAJ
author Meng Chen
Yazhou Cui
Hui Li
Jing Luan
Xiaoyan Zhou
Jinxiang Han
spellingShingle Meng Chen
Yazhou Cui
Hui Li
Jing Luan
Xiaoyan Zhou
Jinxiang Han
Icariin Promotes the Osteogenic Action of BMP2 by Activating the cAMP Signaling Pathway
Molecules
icariin (ica)
osteoblast differentiation
bmp2
camp/pka/creb
author_facet Meng Chen
Yazhou Cui
Hui Li
Jing Luan
Xiaoyan Zhou
Jinxiang Han
author_sort Meng Chen
title Icariin Promotes the Osteogenic Action of BMP2 by Activating the cAMP Signaling Pathway
title_short Icariin Promotes the Osteogenic Action of BMP2 by Activating the cAMP Signaling Pathway
title_full Icariin Promotes the Osteogenic Action of BMP2 by Activating the cAMP Signaling Pathway
title_fullStr Icariin Promotes the Osteogenic Action of BMP2 by Activating the cAMP Signaling Pathway
title_full_unstemmed Icariin Promotes the Osteogenic Action of BMP2 by Activating the cAMP Signaling Pathway
title_sort icariin promotes the osteogenic action of bmp2 by activating the camp signaling pathway
publisher MDPI AG
series Molecules
issn 1420-3049
publishDate 2019-10-01
description Icariin (ICA) is the main active flavonoid glucoside from herbs of the genus <i>Epimedium</i>; in traditional Chinese medicine, these herbs have long been prescribed for the treatment of bone fractures and osteoporosis. Several studies have shown that treatment with ICA can increase osteogenic differentiation and reduce bone loss in vivo and in vitro. However, the definite signaling pathway of this osteogenic effect remains unclear. In this study, we selected bone morphogenetic protein 2 (BMP2)-induced osteoblastic differentiation of multipotent mesenchymal progenitor C2C12 cells as a model of osteoblast differentiation. We investigated the effects of ICA on C2C12 cells osteogenic differentiation and the underlying molecular mechanisms. We found that ICA could enhance BMP2-mediated osteoblastic differentiation of C2C12 cells in a dose-dependent manner. Treatment with ICA activated the cAMP/PKA/CREB signaling axis in a time-dependent manner. Blocking cAMP signaling using the PKA selective inhibitor H89 significantly inhibited the stimulatory effect of ICA on osteogenesis. Therefore, the osteoinductive potential and the low cost of ICA indicate that it is a promising alternative treatment or promoter for enhancing the therapeutic effects of BMP2.
topic icariin (ica)
osteoblast differentiation
bmp2
camp/pka/creb
url https://www.mdpi.com/1420-3049/24/21/3875
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AT huili icariinpromotestheosteogenicactionofbmp2byactivatingthecampsignalingpathway
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