Isopsoralen Enhanced Osteogenesis by Targeting AhR/ERα

被引:50
作者
Ge, Luna [1 ,2 ]
Cui, Yazhou [2 ]
Cheng, Kai [3 ]
Han, Jinxiang [2 ]
机构
[1] Shandong Univ Tradit Chinese Med, Sch Tradit Chinese Med, Jinan 250355, Shandong, Peoples R China
[2] Minist Hlth, Key Lab Biotech Drugs, Shandong Med Biotechnol Ctr, Jinan 250062, Shandong, Peoples R China
[3] Shandong Acad Med Sci, Jinan 250062, Shandong, Peoples R China
关键词
isopsoralen; osteogenesis; aryl hydrocarbon receptor; estrogen receptor alpha; ARYL-HYDROCARBON RECEPTOR; BONE; IDENTIFICATION; SUPPRESSES; PSORALEN; GROWTH; SAFETY; MICE;
D O I
10.3390/molecules23102600
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
070307 [化学生物学]; 071010 [生物化学与分子生物学];
摘要
Isopsoralen (IPRN), one of the main effective ingredients in Psoralea corylifolia Linn, has a variety of biological effects, including antiosteoporotic effects. In vivo studies show that IPRN can increase bone strength and trabecular bone microstructure in a sex hormone deficiency-induced osteoporosis model. However, the mechanism underlying this osteogenic potential has not been investigated in detail. In the present study, we investigated the molecular mechanism of IPRN-induced osteogenesis in MC3T3-E1 cells. Isopsoralen promoted osteoblast differentiation and mineralization, increased calcium nodule levels and alkaline phosphatase (ALP) activity and upregulated osteoblast markers, including ALP, runt-related transcription factor 2 (RUNX2), and collagen type I alpha 1 chain (COL1A1). Furthermore, IPRN limited the nucleocytoplasmic shuttling of aryl hydrocarbon receptor (AhR) by directly binding to AhR. The AhR target gene cytochrome P450 family 1 subfamily A member 1 (CYP1A1) was also inhibited in vitro and in vivo. This effect was inhibited by the AhR agonists indole-3-carbinol (I3C) and 3-methylcholanthrene (3MC). Moreover, IPRN also increased estrogen receptor alpha (ER alpha) expression in an AhR-dependent manner. Taken together, these results suggest that IPRN acts as an AhR antagonist and promotes osteoblast differentiation via the AhR/ER alpha axis.
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页数:11
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