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The flavonol glycoside icariin promotes bone formation in growing rats by activating the cAMP signaling pathway in primary cilia of osteoblasts

文献类型：期刊论文

作者Wei, Zhenlong4; Ma, Huiping3; Xian, Cory J.2; Wang, Jufang1; Chen, Keming4; Shi, Wengui4; Gao, Yuhai4; Wang, Yuanyuan4; Zhou, Jian4; Ma, Xiaoni4
刊名JOURNAL OF BIOLOGICAL CHEMISTRY
出版日期2017-12-22
卷号292页码:20883-20896
ISSN号0021-9258
DOI10.1074/jbc.M117.809517
英文摘要Icariin, a prenylated flavonol glycoside isolated from the herb Epimedium, has been considered as a potential alternative therapy for osteoporosis. Previous research has shown that, unlike other flavonoids, icariin is unlikely to act via the estrogen receptor, but its exact mechanism of action is unknown. In this study, using rat calvarial osteoblast culture and rat bone growth models, we demonstrated that icariin promotes bone formation by activating the cAMP/protein kinase A (PKA)/cAMP response element-binding protein (CREB) pathway requiring functional primary cilia of osteoblasts. We found that icariin increases the peak bone mass attained by young rats and promotes the maturation and mineralization of rat calvarial osteoblasts. Icariin activated cAMP/PKA/CREB signaling of the osteoblasts by increasing intracellular cAMP levels and facilitating phosphorylation of both PKA and CREB. Blocking cAMP/PKA/CREB signaling with inhibitors of the cAMP-synthesizing adenylyl cyclase (AC) and PKA inhibitors significantly inhibited the osteogenic effect of icariin in the osteoblasts. Icariin-activated cAMP/PKA/CREB signaling was localized to primary cilia, as indicated by localization of soluble AC and phosphorylated PKA. Furthermore, blocking ciliogenesis via siRNA knockdown of a cilium assembly protein, IFT88, inhibited icariin-induced PKA and CREB phosphorylation and also abolished icariin's osteogenic effect. Finally, several of these outcomes were validated in icariin-treated rats. Together, these results provide new insights into icariin function and its mechanisms of action and strengthen existing ties between cAMP-mediated signaling and osteogenesis.
WOS关键词SOLUBLE ADENYLYL-CYCLASE ; ESTROGEN-RECEPTOR-ALPHA ; MARROW STROMAL CELLS ; OSTEOGENIC DIFFERENTIATION ; IN-VITRO ; OSTEOCLAST FORMATION ; HERBA-EPIMEDII ; CYCLIC-AMP ; MINERALIZATION ; OSTEOPOROSIS
资助项目National Natural Sciences Foundation of China[81270963] ; National Natural Sciences Foundation of China[81471090] ; National Natural Sciences Foundation of China[81770879] ; International Science & Technology Cooperation Program of China[2015DFR30940] ; Natural Sciences Foundation of Gansu province[1506RJZA307] ; Science and Technology Research Project of Gansu Province[145RTSA012] ; Science and Technology Research Project of Gansu Province[17JR5RA307] ; National Health and Medical Research Council (NHMRC) Australia Senior Research Fellowship[1042105]
WOS研究方向Biochemistry & Molecular Biology
语种英语
WOS记录号WOS:000418453400007
出版者AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
资助机构National Natural Sciences Foundation of China ; International Science & Technology Cooperation Program of China ; Natural Sciences Foundation of Gansu province ; Science and Technology Research Project of Gansu Province ; National Health and Medical Research Council (NHMRC) Australia Senior Research Fellowship
源URL[http://119.78.100.186/handle/113462/46178]  
专题近代物理研究所_生物物理研究室
通讯作者Wang, Jufang; Chen, Keming
作者单位1.Chinese Acad Sci, Inst Modern Phys, Key Lab Space Radiobiol Gansu Prov, Lanzhou 730000, Gansu, Peoples R China
2.Univ South Australia, Sch Pharm & Med Sci, Sansom Inst Hlth Res, Adelaide, SA 5001, Australia
3.CPLA, Lanzhou Gen Hosp, Dept Pharm, Lanzhou 730050, Gansu, Peoples R China
4.CPLA, Lanzhou Gen Hosp, Inst Orthopaed, Lanzhou 730050, Gansu, Peoples R China
推荐引用方式
GB/T 7714		 Wei, Zhenlong,Ma, Huiping,Xian, Cory J.,et al. The flavonol glycoside icariin promotes bone formation in growing rats by activating the cAMP signaling pathway in primary cilia of osteoblasts[J]. JOURNAL OF BIOLOGICAL CHEMISTRY,2017,292:20883-20896.
APA Wei, Zhenlong.,Ma, Huiping.,Xian, Cory J..,Wang, Jufang.,Chen, Keming.,...&Ma, Xiaoni.(2017).The flavonol glycoside icariin promotes bone formation in growing rats by activating the cAMP signaling pathway in primary cilia of osteoblasts.JOURNAL OF BIOLOGICAL CHEMISTRY,292,20883-20896.
MLA Wei, Zhenlong,et al."The flavonol glycoside icariin promotes bone formation in growing rats by activating the cAMP signaling pathway in primary cilia of osteoblasts".JOURNAL OF BIOLOGICAL CHEMISTRY 292(2017):20883-20896.

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来源：近代物理研究所

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