Psoralen and Bakuchiol Ameliorate M-CSF Plus RANKL-Induced Osteoclast Differentiation and Bone Resorption Via Inhibition of AKT and AP-1 Pathways in Vitro

被引:57
作者
Chai, Lijuan [1 ,2 ]
Zhou, Kun [2 ]
Wang, Shaoxia [1 ]
Zhang, Han [1 ,2 ]
Fan, Na [1 ,2 ]
Li, Jie [2 ]
Tan, Xiaofeng [1 ,2 ]
Hu, Limin [1 ,2 ,3 ]
Fan, Xiang [1 ,2 ]
机构
[1] Tianjin Univ Tradit Chinese Med, Minist Educ, Key Lab Pharmacol Tradit Chinese Med Formulae, Tianjin, Peoples R China
[2] Tianjin Univ Tradit Chinese Med, Tianjin Key Lab Tradit Chinese Med Pharmacol, Tianjin, Peoples R China
[3] Tianjin Univ Tradit Chinese Med, Changjiang Scholars & Innovat Res Team Univ, Tianjin, Peoples R China
基金
中国国家自然科学基金;
关键词
Psoralen; Bakuchiol; Osteoclast; Differentiation; Bone resorption; SIGNALING PATHWAYS; OSTEOPOROSIS; EXPRESSION; EXTRACT; MEN; OSTEOBLASTS; INDUCTION; FRACTURE; CELLS; OLDER;
D O I
10.1159/000492554
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Background/Aims: Psoralen and bakuchiol are the main active compounds found in the traditional Chinese medicine Psoralea corylifolia L., and have been used to treat osteoporosis. This study aims to investigate the anti-osteoporosis effects of these two compounds using osteoclasts precursor differentiation and bone absorption assays in vitro. Methods: Primary mouse osteoclasts precursor cells were induced by M-CSF (macrophage colony stimulating factor) plus RANKL (receptor activator of nuclear factor kappa-B ligand) in vitro. TRACP (tartrate-resistant acid phosphatase) enzyme activity and toluidine blue staining were used to observe the effects of psoralen and bakuchiol on osteoclast differentiation and bone resorption, respectively. Gelatin zymography was used to assess MMP (matrix metalloproteinase) activity, and ELISA was performed to measure cathepsin K activity. Western blotting analysis for expression of phosphorylated AKT, ERK, NF-kB, and c-jun; and immunofluorescence analysis for c-jun and p65 nuclear translocation in induced osteoclasts were then used to determine the mechanism of anti-bone resorption of psoralen and bakuchiol. Results: Mature osteoclasts were induced by M-CSF plus RANKL from primary bone marrow macrophages in vitro. Both psoralen and bakuchiol significantly inhibited TRACP enzyme activity and slightly decreased the number of TRACP(+) multinuclear osteoclasts induced by M-CSF plus RANKL. Bakuchiol significantly decreased bone lacunae area and attenuated MMP-2 activity induced by M-CSF plus RANKL in osteoclasts. Both psoralen and bakuchiol significantly decreased the expression and nuclear translocation of phosphorylated c-jun stimulated by M-CSF plus RANKL, but no significant effect on p65 translocation was observed in osteoclasts. Additionally, bakuchiol significantly attenuated the increased of M-CSF plus RANKL-induced phosphorylation of AKT in osteoclasts. Conclusions: Psoralen and bakuchiol ameliorated M-CSF plus RANKL-induced osteoclast differentiation and bone resorption via inhibition of AKT and AP-1 pathways activation in vitro. (C) 2018 The Author(s) Published by S. Karger AG, Basel
引用
收藏
页码:2123 / 2133
页数:11
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