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Ugonin K-stimulated osteogenesis involves estrogen receptor-dependent activation of non-classical Src signaling pathway and classical pathway.

Abstract：

:We have reported previously that ugonin K, a flavonoid isolated from Helminthostachys zeylanica (L.) Hook, potently induces cell differentiation and mineralization of MC3T3-E1 mouse osteoblast-like cells. Here we aimed to elucidate whether ugonin K evoked osteogenesis required interaction with estrogen receptor. Results showed that ugonin K induced increases in alkaline phosphatase (ALP) activity, expressions of bone sialoprotein (BSP) and osteocalcin (OCN), and subsequent bone nodule formation were concentration-dependently inhibited by estrogen receptor antagonist ICI 182,780, suggesting that an estrogen receptor-dependent pathway was involved. In the presence of ICI 182,780, ugonin K induced up-regulation of the expressions of runt-related transcription factor 2 (Runx2) and osterix was also significantly repressed. Numerous studies have demonstrated that estrogens induced rapid and transient activation of the c-Src phosphorylation cascade. We found that ugonin K indeed raised the phosphorylated level of c-Src and such phosphorylation was significantly attenuated by ICI 182,780 treatment. Application of c-Src specific inhibitor PP2 concentration-dependently repressed ugonin K-induced osteogenesis. In the nuclear translocation assay, results showed that ugonin K increased the nuclear level of estrogen receptor-α protein, suggesting that an enhanced transcriptional activity might be observed. Excepting MC3T3-E1 cells, results obtained from ALP activity assay revealed that ugonin K also stimulated osteoblastic differentiation of human MG-63 osteosarcoma cells and rat primary osteoblasts isolated from femora. Our results demonstrate that ugonin K stimulated osteogenesis might act through an estrogen receptor-dependent activation of a non-classical signaling pathway mediated by phosphorylation of c-Src. Moreover, a transactivation potential toward estrogen receptor-α through a classical pathway might not be precluded.

journal_name

Eur J Pharmacol

journal_title

European journal of pharmacology

authors

Lee CH,Huang YL,Liao JF,Chiou WF

doi

10.1016/j.ejphar.2011.12.001

subject

Has Abstract

pub_date

2012-02-15 00:00:00

pages

26-33

issue

1-3

eissn

0014-2999

issn

1879-0712

pii

S0014-2999(11)01519-6

journal_volume

676

pub_type

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Ugonin K-stimulated osteogenesis involves estrogen receptor-dependent activation of non-classical Src signaling pathway and classical pathway.