Amentoflavone enhances osteogenesis of human mesenchymal stem cells through JNK and p38 MAPK pathways
- 607 Downloads
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.
KeywordsHuman mesenchymal stem cells Amentoflavone Osteogenesis JNK and p38 MAPK pathways Osteoporosis
This project was supported by the National Natural Science Foundation of China (30772768, 81102450), Science and Technology Planning Project of Guangdong Province (2013B031800013), Natural Science Foundation of Guangdong Province (2014A030313534), Administration of Traditional Chinese Medicine of Guangdong Province (20151263), Social Science and Technology Development Project of Dongguan (2014108101052), Science and Technology Planning Project for Medical Treatment and Public Health of Dongguan (2014105101294) and Initiating Fund of Scientific Research for Doctors of Guangdong Medical University (B2013016).
Compliance with ethical standards
Conflict of interest
The authors declare no conflict of interest.
- 7.Jiang YH, Jahagirdar BN, Reinhardt RL, Schwartz RE, Keene CD, Ortiz-Gonzalez XR, Reyes M, Lenvik T, Lund T, Blackstad M, Du J, Aldrich S, Lisberg A, Low WC, Largaespada DA, Verfaillie CM (2002) Pluripotency of mesenchymal stem cells derived from adult marrow. Nature 418:41–49CrossRefPubMedGoogle Scholar
- 21.Tarallo V, Lepore L, Marcellini M, Dal Piaz F, Tudisco L, Ponticelli S, Lund FW, Roepstorff P, Orlandi A, Pisano C, De Tommasi N, De Falco S (2011) The biflavonoid amentoflavone inhibits neovascularization preventing the activity of proangiogenic vascular endothelial growth factors. J Biol Chem 286:19641–19651CrossRefPubMedPubMedCentralGoogle Scholar
- 24.Greenblatt MB, Shim JH, Zou W, Sitara D, Schweitzer M, Hu D, Lotinun S, Sano Y, Baron R, Park JM, Arthur S, Xie M, Schneider MD, Zhai B, Gygi S, Davis R, Glimcher LH (2010) The p38 MAPK pathway is essential for skeletogenesis and bone homeostasis in mice. J Clin Investig 120:2457–2473CrossRefPubMedPubMedCentralGoogle Scholar
- 28.Komori T, Yagi H, Nomura S, Yamaguchi A, Sasaki K, Deguchi K, Shimizu Y, Bronson RT, Gao YH, Inada M, Sato M, Okamoto R, Kitamura Y, Yoshiki S, Kishimoto T (1997) Targeted disruption of Cbfa1 results in a complete lack of bone formation owing to maturational arrest of osteoblasts. Cell 89:755–764CrossRefPubMedGoogle Scholar