4.7 Article

Icariin induces osteoblast proliferation, differentiation and mineralization through estrogen receptor-mediated ERK and JNK signal activation

Journal

EUROPEAN JOURNAL OF PHARMACOLOGY
Volume 714, Issue 1-3, Pages 15-22

Publisher

ELSEVIER SCIENCE BV
DOI: 10.1016/j.ejphar.2013.05.039

Keywords

Icariin; Osteoblasts; Mitogen-activated protein kinases; Estrogen receptor; Osteoporosis

Funding

  1. National Natural Science Foundation of China [30872726]

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Icariin, the main active flavonoid glucoside isolated from Herba epimedii (HEF), is an anabolic agent in bone that has been reported to prevent bone loss in ovariectomized rats and postmenopausal women. However, the molecular mechanism for this anabolic action of Icariin remain largely unknown. Here, we found that Icariin could promote MC3T3-E1 osteoblastic cell proliferation and reduce cell apoptosis, associated with increased mRNA levels of positive regulators of cell cycle gene Cyclin E and proliferating cell nuclear antigen (PCNA), decreaed mRNA level of negative regulator gene, Cyclin-dependent kinase 4 inhibitor B (Cdkn2B), and reduced caspase-3 activity. Icariin also enhanced MC3T3-E1 cell differentiation and mineralization demonstrated by increased the expression of differentiation markers, alkaline phosphatase (ALP) and collagen type I (Col I), and bone nodule formation via Alizarin red S staining. To characterize the underlying mechanisms, we examined the effect of Icariin on mitogen-activated protein kinase (MAPK) signaling. Icariin treatment rapidly induced extracellular signal-regulated kinase (ERK) and c-Jun N terminal kinase (JNK) activation but showed no effect on activation of p38 kinase. Furthermore, Icariin-mediated effects on osteoblasts were dramatically attenuated by treatment with specific inhibitors of MAPKs, U0126 (ERK inhibitor) and SP600125 (JNK inhibitor). Interestingly, treatment of osteoblasts with estrogen receptor antagonist ICI182780 attenuated Icariin-mediated effect of proliferation and mineralization, associated with suppression of ERK and JNK phosphorylation. These observations provide a potential mechanism of anabolic actions of Icariin involving ERK and JNK pathway by estrogen receptor. (c) 2013 Elsevier B.V. All rights reserved.

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