Amentoflavone enhances osteogenesis of human mesenchymal stem cells through JNK and p38 MAPK pathways

Abstract

Amentoflavone is a bioflavonoid found in a variety of traditional Chinese medicines such as Gingko and Selaginella tamariscina. It has been reported that amentoflavone has anti-inflammatory, antioxidant, antiviral and anticancer effects. However, the effect of amentoflavone on osteogenic differentiation of human mesenchymal stem cells (hMSCs) has not been studied. In this study, we aim to explore the effect of amentoflavone on the proliferation and osteogenic differentiation of hMSCs. The results showed that amentoflavone significantly enhanced the proliferation, alkaline phosphatase (ALP) activity and mineralization in hMSCs. Western blot analysis revealed that the expression of runt-related transcription factor 2 and osterix proteins was upregulated in amentoflavone-treated hMSCs. Furthermore, we investigated the possible signaling pathways responsible for osteogenic differentiation of hMSCs by amentoflavone. We found that amentoflavone significantly increased the levels of phosphorylated JNK and p-p38. The amentoflavone-induced increases of ALP and mineralization were significantly diminished when the JNK and p38 MAPK pathways were blocked by selected inhibitors (SP600125, SB203580) in hMSCs. Furthermore, in vivo evidence indicated that amentoflavone protected against the dexamethasone-induced inhibition of osteoblast differentiation in tg(sp7:egfp) zebrafish larvae. Thus, we showed for the first time that amentoflavone improves the osteogenesis of hMSCs through the JNK and p38 MAPK pathway. Amentoflavone may be beneficial in treating bone-related disorders.

Anticytotoxin Effects of Amentoflavone to Pneumolysin

“…[8][9][10][11] Drug screening verified this natural flavonoid compound. A hemolysis assay determined its effectiveness in inhibiting the hemolytic activity of pneumolysin.…”

“…It has many beneficial biological properties, including enhancement of osteogenesis, protection against radiation, as well as anti-human immunodeficiency virus (HIV), anti-inflammatory, anti-oxidative, and anti-apoptotic effects. [8][9][10][11] However, as far as we know the antivirulence effects of AMF on PLY-mediated cytotoxicity have not been examined. To determine the molecular mechanisms of AMF antivirulence function, homology modeling and molecular docking studies were carried out on protein mutants of the PLY-AMF complex.…”

Human Cord Blood‐Derived CD133+/C‐Kit+/Lin− Cells Have Bipotential Ability to Differentiate into Mesenchymal Stem Cells and Outgrowth Endothelial Cells

“…To overcome this hurdle, a better understanding of the primitive cell population in umbilical cord blood is imperative for optimizing cell expansion. Furthermore, although the differentiation capacity of cord blood MNCs has been extensively studied [18–20], little is known about whether MNCs have the pluripotent capacity to differentiate into MSCs or OECs or are a mixture of progenitor cells with determined MSC or OEC fates.…”

Osteogenic Effect of Inducible Nitric Oxide Synthase (iNOS)-Loaded Mineralized Nanoparticles on Embryonic Stem Cells

“…Among the activated pathways, MAPK signaling pathways promote the osteogenesis of stem cells in other experimental systems. Osteogenesis in human mesenchymal stem cells was improved by bioflavonoid treatment through the activation of c-Jun N-terminal kinase (JNK) and p38 MAPK pathways [37]. Inorganic nanoparticles such as those composed of gold or iron stimulate the osteogenesis of human periodontal ligament stem cells (PDLSCs) or human bone marrow stromal cells (BMSCs) in vitro via the p38 MAPK or extracellular signal-regulated kinase 1/2 (ERK1/2) activation [38,39].…”