Amentoflavone enhances osteogenesis of human mesenchymal stem cells through JNK and p38 MAPK pathways.
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.
Department of Pharmacology, Guangdong Medical University, 523808, Dongguan, China.
Xuan
X
Zha
Department of Pharmacology, Guangdong Medical University, 523808, Dongguan, China.
Zhoumei
Z
Xu
Department of Pharmacology, Guangdong Medical University, 523808, Dongguan, China.
Yuyu
Y
Liu
Department of Orthopaedics and Traumatology, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong, China.
Liangliang
L
Xu
Affiliated Hospital of Guangdong Medical University, 524023, Zhanjiang, China.
Hongxin
H
Huang
Affiliated Hospital of Guangdong Medical University, 524023, Zhanjiang, China.
Jingjing
J
Zhang
Department of Pharmacology, Guangdong Medical University, 523808, Dongguan, China.
Liao
L
Cui
School of Nursing, Guangdong Medical University, 523808, Dongguan, China. Chenhuizh22@163.com.
Chenhui
C
Zhou
Department of Pharmacology, Guangdong Medical University, 523808, Dongguan, China. daohuax108@163.com.|Institution of Traditional Chinese Medicine and New Pharmacy Development, Guangdong Medical University, 523808, Dongguan, China. daohuax108@163.com.|Guangdong Key Laboratory for Research and Development of Natural Drugs, Guangdong Medical University, 524023, Zhanjiang, China. daohuax108@163.com.
Daohua
D
Xu
D044946:Biflavonoids / Q000008:administration & dosage / Q000627:therapeutic use*; D002454:Cell Differentiation; D049109:Cell Proliferation; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000187:drug effects*; D010012:Osteogenesis / Q000187:drug effects*; D010024:Osteoporosis / Q000188:drug therapy*; D015398:Signal Transduction; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
D044946:Biflavonoids; C011164:amentoflavone; D048051:p38 Mitogen-Activated Protein Kinases
Amentoflavone; Human mesenchymal stem cells; JNK and p38 MAPK pathways; Osteogenesis; Osteoporosis