1. Academic Validation
  2. Isopsoralen Enhanced Osteogenesis by Targeting AhR/ERα

Isopsoralen Enhanced Osteogenesis by Targeting AhR/ERα

  • Molecules. 2018 Oct 11;23(10):2600. doi: 10.3390/molecules23102600.
Luna Ge 1 2 Yazhou Cui 3 Kai Cheng 4 Jinxiang Han 5
Affiliations

Affiliations

  • 1 School of Traditional Chinese Medicine, Shandong University of Traditional Chinese Medicine, Jinan 250355, China. geluna606@163.com.
  • 2 Shandong Medicinal Biotechnology Center, Key Laboratory for Biotech-Drugs of the Ministry of Health, Jinan 250062, China. geluna606@163.com.
  • 3 Shandong Medicinal Biotechnology Center, Key Laboratory for Biotech-Drugs of the Ministry of Health, Jinan 250062, China. cuiyz15@126.com.
  • 4 Shandong Academy of Medical Sciences, Jinan 250062, China. chengkai606@163.com.
  • 5 Shandong Medicinal Biotechnology Center, Key Laboratory for Biotech-Drugs of the Ministry of Health, Jinan 250062, China. samshjx88@sina.com.
Abstract

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 (ERα) 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/ERα axis.

Keywords

aryl hydrocarbon receptor; estrogen receptor alpha; isopsoralen; osteogenesis.

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