Quercetin promotes the osteogenic differentiation of rat mesenchymal stem cells via mitogen-activated protein kinase signaling

Li,Yang; Wang,Jiefang; Chen,Guangming; Feng,Shuiwang; Wang,Panpan; Zhu,Xiaofeng; Zhang,Ronghua

doi:10.3892/etm.2015.2388

Quercetin promotes the osteogenic differentiation of rat mesenchymal stem cells via mitogen-activated protein kinase signaling

Authors:
- Yang Li
- Jiefang Wang
- Guangming Chen
- Shuiwang Feng
- Panpan Wang
- Xiaofeng Zhu
- Ronghua Zhang
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Affiliations: Department of Traditional Chinese Medicine, College of Pharmacy, Jinan University, Guangzhou, Guangdong 510632, P.R. China, Department of Traditional Chinese Medicine, First Affiliated Hospital of Jinan University, Jinan University, Guangzhou, Guangdong 510632, P.R. China
Published online on: March 26, 2015 https://doi.org/10.3892/etm.2015.2388
Pages: 2072-2080
Copyright: © Li et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

The aim of the present study was to investigate the effects of quercetin on the mitogen-activated protein kinase (MAPK) signaling pathway in the osteogenic differentiation of rat mesenchymal stem cells (MSCs). A 3-(4,5‑dimethylthiazol‑2‑yl)‑2,5‑diphenyltetrazolium bromide assay and an alkaline phosphatase (ALP) assay were used to determine the effects of quercetin (concentrations of 0.1, 1 and 10 µmol/l) on the proliferation and differentiation of MSCs and the expression of ALP, respectively. In addition, through the introduction of inhibitors of p38 MAPK, extracellular signal‑regulated kinase (ERK)1/2 and c‑Jun NH2‑terminal kinase (JNK), the effects of quercetin on the proteins, ALP, collagen type I (COL I) and bone γ‑carboxyglutamate protein (BGP), which are indicators of osteogenic differentiation, were investigated. Immunoblotting was performed to determine the phosphorylation levels of p38 MAPK, ERK1/2 and JNK, while fluorescent quantitative polymerase chain reaction was used to determine the mRNA expression levels of transforming growth factor (TGF)‑β1, bone morphogenetic protein (BMP)‑2 and core binding factor (CBF)α1. At all the concentrations tested, the concentrations of 10, 1 and 0.1 µmol/l quercetin were shown to promote the differentiation of MSCs and the expression of ALP, in which the concentration of 10 µmol/l was optimal. When compared with the control group, the phosphorylation levels of p38 MAPK, ERK1/2 and JNK, the protein expression levels of ALP, COL I and BGP, and the mNRA expression levels of TGF‑β1, BMP‑2 and Cbfα1 were increased in the quercetin‑treated group. However, with the introduction of inhibitors, the levels of phosphorylated p38 MAPK, ERK1/2 and JNK, and the protein expression levels of ALP, COL I and BGP decreased. Furthermore, the mRNA expression levels of TGF‑β1, BMP‑2 and CBFα1 decreased in the quercetin + SP600125 (inhibitor of JNK) and quercetin + PD98059 (inhibitor of ERK1/2) groups. Therefore, quercetin was demonstrated to promote the osteogenic differentiation of MSCs by activating the MAPK signaling pathway. The ERK1/2 and JNK signaling pathways regulate the expression of TGF‑β1, BMP‑2 and CBFα1. Thus, activation of the ERK1/2 and JNK signaling pathways may play a leading role in the quercetin‑promoted osteogenic proliferation and differentiation of MSCs.

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