caa a22 4500 606235558 CHVBK 20210128101243.0 cr unu---uuuuu 210128e20150901xx s 000 0 eng 10.1007/s11010-015-2452-9 doi (NATIONALLICENCE)springer-10.1007/s11010-015-2452-9 Apigenin promotes osteogenic differentiation of human mesenchymal stem cells through JNK and p38 MAPK pathways [Elektronische Daten] [Xue Zhang, Chenhui Zhou, Xuan Zha, Zhoumei Xu, Li Li, Yuyu Liu, Liangliang Xu, Liao Cui, Daohua Xu, Baohua Zhu] 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 promotesthe 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. Springer Science+Business Media New York, 2015 Apigenin nationallicence Mesenchymal stem cell nationallicence Osteogenesis nationallicence Osteoporosis nationallicence JNK and p38 MAPK signaling pathway nationallicence Zhang Xue Department of Pharmacology, Guangdong Medical University, Dongguan, China aut Zhou Chenhui School of Nursing, Guangdong Medical University, Dongguan, China aut Zha Xuan Department of Pharmacology, Guangdong Medical University, Dongguan, China aut Xu Zhoumei Department of Pharmacology, Guangdong Medical University, Dongguan, China aut Li Li Institution of Traditional Chinese Medicine and New Pharmacy Development, Guangdong Medical University, Dongguan, China aut Liu Yuyu Department of Pharmacology, Guangdong Medical University, Dongguan, China aut Xu Liangliang Department of Orthopaedics & Traumatology, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong, China aut Cui Liao Department of Pharmacology, Guangdong Medical University, Dongguan, China aut Xu Daohua Department of Pharmacology, Guangdong Medical University, Dongguan, China aut Zhu Baohua The Second Clinical School, Guangdong Medical University, Dongguan, China aut Molecular and Cellular Biochemistry Springer US; http://www.springer-ny.com 407/1-2(2015-09-01), 41-50 0300-8177 407:1-2<41 2015 407 11010 https://doi.org/10.1007/s11010-015-2452-9 text/html Onlinezugriff via DOI BK010053 XK010053 XK010000 Metadata rights reserved Springer special CC-BY-NC licence nationallicence 1 research-article jats NATIONALLICENCE NATIONALLICENCE NL-springer NATIONALLICENCE 856 40 https://doi.org/10.1007/s11010-015-2452-9 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Zhang Xue Department of Pharmacology, Guangdong Medical University, Dongguan, China aut NATIONALLICENCE 700 1- Zhou Chenhui School of Nursing, Guangdong Medical University, Dongguan, China aut NATIONALLICENCE 700 1- Zha Xuan Department of Pharmacology, Guangdong Medical University, Dongguan, China aut NATIONALLICENCE 700 1- Xu Zhoumei Department of Pharmacology, Guangdong Medical University, Dongguan, China aut NATIONALLICENCE 700 1- Li Li Institution of Traditional Chinese Medicine and New Pharmacy Development, Guangdong Medical University, Dongguan, China aut NATIONALLICENCE 700 1- Liu Yuyu Department of Pharmacology, Guangdong Medical University, Dongguan, China aut NATIONALLICENCE 700 1- Xu Liangliang Department of Orthopaedics & Traumatology, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong, China aut NATIONALLICENCE 700 1- Cui Liao Department of Pharmacology, Guangdong Medical University, Dongguan, China aut NATIONALLICENCE 700 1- Xu Daohua Department of Pharmacology, Guangdong Medical University, Dongguan, China aut NATIONALLICENCE 700 1- Zhu Baohua The Second Clinical School, Guangdong Medical University, Dongguan, China aut NATIONALLICENCE 773 0- Molecular and Cellular Biochemistry Springer US; http://www.springer-ny.com 407/1-2(2015-09-01), 41-50 0300-8177 407:1-2<41 2015 407 11010