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

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Abstract

Apigenin is a plant-derived flavonoid and has been reported to prevent bone loss in ovariectomized mice, but the role of apigenin on osteogenic differentiation of human mesenchymal stem cells (hMSCs) has not been reported. In the present study, the effect of apigenin on osteogenic differentiation of hMSCs was explored. Our results showed that apigenin treatment significantly increased alkaline phosphatase (ALP) activity and mineralization in hMSCs. RT-PCR revealed that apigenin markedly up-regulated the mRNA expression of osteopontin (OPN) and the transcription factors runt-related transcription factor 2 (Runx2). The expression of Runx2 and osterix (OSX) proteins were also increased in hMSCs differentiating into osteoblasts after treatment with apigenin. Furthermore, we investigated the signaling pathways responsible for osteogenic differentiation of apigenin in hMSCs. We found that apigenin treatment significantly increased the levels of p-JNK, p-p38 in hMSCs and addition of the inhibitors of JNK (SP600125) or p38 MAPK (SB203580) eliminated the stimulating effects of apigenin. In addition, addition of SP600125 or SB203580 also blocked apigenin-induced ALP activity, OPN, Runx2, and OSX expression and meanwhile inhibited bone nodule formation. Taken together, these findings suggest apigenin promotes the osteogenesis of hMSCs through activation of JNK and p38 MAPK signal pathways which leads to Runx2 and OSX expressions to induce the formation of bone nodule.

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Acknowledgments

We thank financial support from National Natural Science Foundation of China (30772768, 81102450), Science and Technology Planning Project of Guangdong Province (2013B031800013); Natural Science Foundation of Guangdong Province (2014A030313534); 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).

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The authors declare no conflict of interest.

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    Authors and Affiliations

    1. Department of Pharmacology, Guangdong Medical University, Dongguan, China

      Xue Zhang, Xuan Zha, Zhoumei Xu, Yuyu Liu, Liao Cui & Daohua Xu

    2. School of Nursing, Guangdong Medical University, Dongguan, China

      Chenhui Zhou

    3. Institution of Traditional Chinese Medicine and New Pharmacy Development, Guangdong Medical University, Dongguan, China

      Li Li & Daohua Xu

    4. Department of Orthopaedics & Traumatology, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong, China

      Liangliang Xu

    5. The Second Clinical School, Guangdong Medical University, Dongguan, China

      Baohua Zhu

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    Xue Zhang, Chenhui Zhou and Xuan Zha have contributed equally to this work.

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    Zhang, X., Zhou, C., Zha, X. et al. Apigenin promotes osteogenic differentiation of human mesenchymal stem cells through JNK and p38 MAPK pathways. Mol Cell Biochem 407, 41–50 (2015). https://doi.org/10.1007/s11010-015-2452-9

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