title: Anti-osteoclastogenic activity of praeruptorin A via inhibition of p38/Akt-c-Fos-NFATc1 signaling and PLCγ-independent Ca2+ oscillation.
abstract: BACKGROUND
  A decrease of bone mass is a major risk factor for fracture. Several natural products have traditionally been used as herbal medicines to prevent and/or treat bone disorders including osteoporosis. Praeruptorin A is isolated from the dry root extract of Peucedanum praeruptorum Dunn and has several biological activities, but its anti-osteoporotic activity has not been studied yet.
  
  
  METHODS
  The effect of praeruptorin A on the differentiation of bone marrow-derived macrophages into osteoclasts was examined by phenotype assay and confirmed by real-time PCR and immunoblotting. The involvement of NFATc1 in the anti-osteoclastogenic action of praeruptorin A was evaluated by its lentiviral ectopic expression. Intracellular Ca(2+) levels were also measured.
  
  
  RESULTS
  Praeruptorin A inhibited the RANKL-stimulated osteoclast differentiation accompanied by inhibition of p38 and Akt signaling, which could be the reason for praeruptorin A-downregulated expression levels of c-Fos and NFATc1, transcription factors that regulate osteoclast-specific genes, as well as osteoclast fusion-related molecules. The anti-osteoclastogenic effect of praeruptorin A was rescued by overexpression of NFATc1. Praeruptorin A strongly prevented the RANKL-induced Ca(2+) oscillation without any changes in the phosphorylation of PLCγ.
  
  
  CONCLUSIONS
  Praeruptorin A could exhibit its anti-osteoclastogenic activity by inhibiting p38/Akt-c-Fos-NFATc1 signaling and PLCγ-independent Ca(2+) oscillation.
authors.affiliation: Research Institute of Basic Science, Sunchon National University, Suncheon, Republic of Korea.
authors.forename: Jeong-Tae
authors.initials: JT
authors.lastname: Yeon
authors.affiliation: Research Institute of Basic Science, Sunchon National University, Suncheon, Republic of Korea.
authors.forename: Kwang-Jin
authors.initials: KJ
authors.lastname: Kim
authors.affiliation: Laboratory of Translational Therapeutics, Pharmacology Research Center, Division of Drug Discovery Research, Korea Research Institute of Chemical Technology, Daejeon, Republic of Korea.
authors.forename: Sik-Won
authors.initials: SW
authors.lastname: Choi
authors.affiliation: Laboratory of Translational Therapeutics, Pharmacology Research Center, Division of Drug Discovery Research, Korea Research Institute of Chemical Technology, Daejeon, Republic of Korea ; Department of Biology, Chungnam National University, Daejeon, Republic of Korea.
authors.forename: Seong-Hee
authors.initials: SH
authors.lastname: Moon
authors.affiliation: Herbal Medicine Research Division, National Institute of Food & Drug Safety Evaluation, Cheongwon, Republic of Korea ; Graduate School of New Drug Discovery and Development, Chungnam National University, Daejeon, Republic of Korea.
authors.forename: Young Sik
authors.initials: YS
authors.lastname: Park
authors.affiliation: Laboratory of Translational Therapeutics, Pharmacology Research Center, Division of Drug Discovery Research, Korea Research Institute of Chemical Technology, Daejeon, Republic of Korea.
authors.forename: Byung Jun
authors.initials: BJ
authors.lastname: Ryu
authors.affiliation: Department of Anatomy & Institute for Skeletal Diseases, School of Medicine, Wongkwang University, Iksan, Republic of Korea.
authors.forename: Jaemin
authors.initials: J
authors.lastname: Oh
authors.affiliation: Department of Oral Physiology, School of Dentistry, Wongkwang University, Iksan, Republic of Korea.
authors.forename: Min Seuk
authors.initials: MS
authors.lastname: Kim
authors.affiliation: Department of Oral Physiology, School of Dentistry, Wongkwang University, Iksan, Republic of Korea.
authors.forename: Munkhsoyol
authors.initials: M
authors.lastname: Erkhembaatar
authors.affiliation: Research Institute of Basic Science, Sunchon National University, Suncheon, Republic of Korea.
authors.forename: Young-Jin
authors.initials: YJ
authors.lastname: Son
authors.affiliation: Laboratory of Translational Therapeutics, Pharmacology Research Center, Division of Drug Discovery Research, Korea Research Institute of Chemical Technology, Daejeon, Republic of Korea ; Graduate School of New Drug Discovery and Development, Chungnam National University, Daejeon, Republic of Korea.
authors.forename: Seong Hwan
authors.initials: SH
authors.lastname: Kim
mesh_terms: D000135:Acid Phosphatase; D002118:Calcium / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects*; D003374:Coumarins / Q000737:chemistry / Q000494:pharmacology*; D017931:DNA Primers / Q000235:genetics; D006801:Humans; D015151:Immunoblotting; D007527:Isoenzymes; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D008264:Macrophages / Q000166:cytology* / Q000187:drug effects; D015394:Molecular Structure; D050778:NFATC Transcription Factors / Q000378:metabolism; D051058:Oncogene Protein v-akt / Q000378:metabolism; D010010:Osteoclasts / Q000166:cytology* / Q000187:drug effects; D010024:Osteoporosis / Q000517:prevention & control*; D051966:Phospholipase C gamma / Q000378:metabolism; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D000071681:Tartrate-Resistant Acid Phosphatase
chemical_list: D003374:Coumarins; D017931:DNA Primers; D007527:Isoenzymes; D050778:NFATC Transcription Factors; C494003:NFATC1 protein, human; D016760:Proto-Oncogene Proteins c-fos; C441070:praeruptorin A; D051058:Oncogene Protein v-akt; D000135:Acid Phosphatase; D000071681:Tartrate-Resistant Acid Phosphatase; D051966:Phospholipase C gamma; D002118:Calcium