title: Attenuation of RANKL-induced Osteoclast Formation via p38-mediated NFATc1 Signaling Pathways by Extract ofEuphorbia LathyrisL.
abstract: BACKGROUND
  Osteoclasts are the only cell type capable of breaking down bone matrix, and its excessive activation is responsible for the development of bone-destructive diseases.Euphorbia lathyrisL. (ELL) is an herbal plant that belongs to the Euphorbiaceae family. This study investigated the effects of the methanol extract of the aerial part of ELL on receptor activator of nuclear factor-kappa B ligand (RANKL)-induced osteoclast formation and signaling pathways.
  
  
  METHODS
  Osteoclasts were formed by co-culturing mouse bone marrow with osteoblasts or by culturing mouse bone marrow-derived macrophages (BMMs) with macrophage colony-stimulating factor (M-CSF) and RANKL. Bone resorption assays were performed using dentine slices. The expression level of mRNA was analyzed by real-time polymerase chain reaction (PCR) or reverse transcription (RT)-PCR. Western blotting assays were performed to detect the expression or activation level of proteins.
  
  
  RESULTS
  ELL inhibited RANKL-induced osteoclast formation without cytotoxicity. Furthermore, the RANKL-stimulated bone resorption was diminished by ELL. Mechanistically, ELL blocked the RANKL-triggered p38 mitogen-activated protein kinase (MAPK) phosphorylation, which resulted in the suppression of the expression of c-Fos and nuclear factor of activated T cells (NFATc1). In osteoblasts, ELL had little effect on the mRNA expression of RANKL and osteoprotegerin (OPG).
  
  
  CONCLUSIONS
  The present data suggest that ELL has an inhibitory effect on osteoclast differentiation and function via downregulation of the p38/c-Fos/NFATc1 signaling pathways. Thus, ELL could be useful for the treatment of bone diseases associated with excessive bone resorption.
authors.affiliation: College of Pharmacy, Sookmyung Women's University, Seoul, Korea.
authors.forename: Ju-Hee
authors.initials: JH
authors.lastname: Kang
authors.affiliation: College of Pharmacy, Sookmyung Women's University, Seoul, Korea.
authors.forename: Hyojung
authors.initials: H
authors.lastname: Lim
authors.affiliation: College of Pharmacy, Sookmyung Women's University, Seoul, Korea.
authors.forename: Ji-Eun
authors.initials: JE
authors.lastname: Jeong
authors.affiliation: College of Pharmacy, Sookmyung Women's University, Seoul, Korea.
authors.forename: Mijung
authors.initials: M
authors.lastname: Yim
keywords: Euphorbia; Genes fos; Nfatc1 protein mouse; Osteoclasts; p38 mitogen-activated protein kinases