Apigenin promotes osteogenic differentiation of human mesenchymal stem cells through JNK and p38 MAPK pathways

Zhang, Xue; Zhou, Chenhui; Zha, Xuan; Xu, Zhoumei; Li, Li; Liu, Yuyu; Xu, Liangliang; Cui, Liao; Xu, Daohua; Zhu, Bin

doi:10.1007/s11010-015-2452-9

Cited by 58 publications

(41 citation statements)

References 41 publications

(51 reference statements)

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“…Our data demonstrated that osteoblastic cells treatment with apigenin and luteolin at a concentration of 1 μ M significantly increased the transcriptional level of COL-I, OPN, and OCN (Figure 9(a)). Similar concentrations of these two compounds have been used, and our findings are in agreement with the other experiments [26–28]. In a previous study, we reported that linarin extracted from FCI enhanced the osteoblast differentiation in MC3T3-E1 cells in a dose-dependent manner [11].…”

Section: Resultssupporting

confidence: 92%

Preparative Purification of Bioactive Compounds fromFlos Chrysanthemi Indiciand Evaluation of Its Antiosteoporosis Effect

Lin

Zhang

et al. 2016

Evidence-Based Complementary and Alternative Medicine

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To understand the material basis and underlying molecular machinery of antiosteoporosis activity of the Flos Chrysanthemi Indici (FCI), the consequences of ethanol extract on the bone loss in mice induced due to ovariectomy (OVX) was evaluated. Also, the antiosteoporosis fraction obtained from the FCI ethanol extract was isolated and purified using a preparative high-speed countercurrent chromatography (HSCCC). The in vitro impact of the compounds was investigated on osteoblast proliferation and differentiation. The results revealed that ethyl acetate fraction with robust in vivo antiosteoporosis activity was obtained. The important compounds purified by HSCCC using gradient elution system included acacetin, apigenin, luteolin, and linarin. The four compounds enhanced the differentiation and proliferation of osteoblasts in MC3T3-E1 cells. They also augmented the mRNA levels of runt-related transcription factor 2 (Runx2), osteocalcin (OCN), osteopontin (OPN), and type I collagen (COL I). The AKT signaling pathway was also activated in MC3T3-E1 cells by the four compounds. The present study demonstrated that the antiosteoporosis effects of FCI did not depend on a single component, and HSCCC efficiently isolated and purified the antiosteoporosis bioactive compounds from FCI.

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Section: Resultssupporting

confidence: 92%

Preparative Purification of Bioactive Compounds fromFlos Chrysanthemi Indiciand Evaluation of Its Antiosteoporosis Effect

Lin

Zhang

et al. 2016

Evidence-Based Complementary and Alternative Medicine

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“…34 It has been reported that the activation of JNK and p38 leads to Runx-2 and Osterix expression, and promotes MSCs osteogenesis. 35 In the present study, IL-7 significantly reduced the phosphorylated levels of JNK, ERK1/2, and p38, which indicated IL-7 inhibited osteogenic differentiation of PDLSCs possibly through inactivation of MAPK signaling pathway. It should be noted that there are some limitations in this study.…”

Section: Il-7 Inhibits Osteogenic Differentiation Of Pdlscssupporting

confidence: 63%

IL-7 suppresses osteogenic differentiation of periodontal ligament stem cells through inactivation of mitogen-activated protein kinase pathway

Cao

Fan²,

Yonghe³

et al. 2016

Organogenesis

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ABSTRACT. Periodontal ligament stem cells (PDLSCs) are tissue-specific mesenchymal stem cells (MSCs), having an important role in regenerative therapy for teeth loss. Interleukin-7 (IL-7) is a key cytokine produced by stromal cells including MSCs, and exhibits specific roles for B and T cell development and osteoblasts differentiation of multiple myeloma. However, the effect of IL-7 on osteogenic differentiation of PDLSCs remains unclear. Therefore, in the present study we determined whether IL-7 affects the proliferation and osteogenic differentiation of PDLSCs in vitro and explored the associated signaling pathways for IL-7-mediated cell differentiation. The results demonstrated that the isolated human PDLSCs possessed MSCs features, highly expressing CD90, CD44, CD105, CD29 and CD73, and almost did not expressed CD34, CD45, CD11b, CD14 and CD117. IL-7 could not significantly affect the proliferation of PDLSCs, but it decreased their osteogenic differentiation and inhibited alkaline phosphatase (ALP) activity. The results of quantitative reverse transcriptionpolymerase chain reaction (qRT-PCR) and Western blotting exhibited that the expression levels of Runx-2, SP7 and osteocalcin (OCN) were significantly reduced by IL-7. Further studies indicated that IL-7 did not significantly change JNK, ERK1/2 and p38 protein production, but markedly suppressed their phosphorylation levels. These data suggest that IL-7 inhibits the osteogenic differentiation of PDLSCs probably via inactivation of mitogen-activated protein kinase (MAPK) signaling pathway.

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“…Moreover, JNK inhibition was found to prevent the neuronal differentiation of mouse embryonic stem cells [24]. The activities of JNK and p38 are required for the differentiation of MSCs to osteocytes [25]. …”

Section: Introductionmentioning

confidence: 99%

ERK signaling is required for VEGF-A/VEGFR2-induced differentiation of porcine adipose-derived mesenchymal stem cells into endothelial cells

Almalki

Agrawal

2017

Stem Cell Res Ther

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BackgroundCell-based therapy that can rejuvenate the endothelium with stimulated adipose-derived mesenchymal stem cells (AMSCs) is a promising therapeutic strategy for the re-endothelialization of denuded arteries at the stenting site. Previously, we have shown that silencing of MMP-2 and MMP-14 inhibits vascular endothelial growth factor receptor type 2 (VEGFR2) cleavage, and induces differentiation of AMSCs toward the endothelial cell (EC) lineage. In this study, we examined the underlying signaling pathways that regulate differentiation of AMSCs to ECs in vitro through VEGFR2.MethodsAMSCs were isolated from porcine abdominal adipose tissue. The isolated AMSCs were characterized by positive expression of CD29, CD44, and CD90 and negative expression of CD11b and CD45. The isolated MSCs were transfected with siRNA to silence MMP-2, MMP-14, and angiotensin receptor 2 (ATR2). Cells were suspended either in endothelial basal media (EBM) or endothelial growth media (EGM) with various treatments. Flow cytometry was performed to examine the expression of EC markers, and western blot analysis was performed to examine the expression and activity of various kinases. Scratch assay was performed to examine the cell migration. Data were analyzed by ANOVA using PRISM GraphPad.ResultsAfter 10 days of stimulation for EC differentiation, the morphology of AMSCs changed to a morphology similar to that of ECs. Silencing MMP-2 and MMP-14 resulted in significant decrease in the number of migrated cells compared with the EGM-only group. ATR2 siRNA transfection did not affect the migration and differentiation of AMSCs to ECs. Stimulation of AMSCs for EC differentiation with or without MMP-2 or MMP-14 siRNA resulted in significant increase in p-ERK, and significant decrease in p-JNK. There was no significant change in p-p38 in all three groups compared with the EBM group. ERK inhibition resulted in significant decrease in the expression of EC markers in the EGM, EGM + MMP-2 siRNA, and EGM + MMP-14 siRNA groups. The VEGFR2 kinase inhibitor induced a dose-dependent inhibition of ERK.ConclusionThe ERK signaling pathway is critical for VEGF-A/VEGFR2-induced differentiation of AMSCs into ECs. These findings provide new insights into the role of the ERK signaling pathway in AMSC differentiation to ECs for potential clinical use in cardiovascular diseases.

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Apigenin promotes osteogenic differentiation of human mesenchymal stem cells through JNK and p38 MAPK pathways

Cited by 58 publications

References 41 publications

Preparative Purification of Bioactive Compounds fromFlos Chrysanthemi Indiciand Evaluation of Its Antiosteoporosis Effect

Preparative Purification of Bioactive Compounds fromFlos Chrysanthemi Indiciand Evaluation of Its Antiosteoporosis Effect

IL-7 suppresses osteogenic differentiation of periodontal ligament stem cells through inactivation of mitogen-activated protein kinase pathway

ERK signaling is required for VEGF-A/VEGFR2-induced differentiation of porcine adipose-derived mesenchymal stem cells into endothelial cells

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