title: Apigenin promotes osteogenic differentiation of human mesenchymal stem cells through JNK and p38 MAPK pathways.
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.
authors.affiliation: Department of Pharmacology, Guangdong Medical University, Dongguan, China.
authors.forename: Xue
authors.initials: X
authors.lastname: Zhang
authors.forename: Chenhui
authors.initials: C
authors.lastname: Zhou
authors.forename: Xuan
authors.initials: X
authors.lastname: Zha
authors.forename: Zhoumei
authors.initials: Z
authors.lastname: Xu
authors.forename: Li
authors.initials: L
authors.lastname: Li
authors.forename: Yuyu
authors.initials: Y
authors.lastname: Liu
authors.forename: Liangliang
authors.initials: L
authors.lastname: Xu
authors.forename: Liao
authors.initials: L
authors.lastname: Cui
authors.forename: Daohua
authors.initials: D
authors.lastname: Xu
authors.forename: Baohua
authors.initials: B
authors.lastname: Zhu
mesh_terms: D000469:Alkaline Phosphatase / Q000378:metabolism; D047310:Apigenin / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D050659:Core Binding Factor Alpha 1 Subunit / Q000235:genetics; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000187:drug effects*; D010012:Osteogenesis / Q000187:drug effects*; D053495:Osteopontin / Q000235:genetics
chemical_list: D050659:Core Binding Factor Alpha 1 Subunit; C493709:RUNX2 protein, human; D053495:Osteopontin; D047310:Apigenin; D000469:Alkaline Phosphatase