title: Decursin from Angelica gigas suppresses RANKL-induced osteoclast formation and bone loss.
abstract: Osteoclasts are the only cells capable of breaking down bone matrix, and excessive activation of osteoclasts is responsible for bone-destructive diseases. In this study, we investigated the effects of decursin from extract of Angelica gigas root on receptor activator of nuclear factor kappa B ligand (RANKL)-induced osteoclast formation using mouse bone marrow-derived macrophages (BMMs). Decursin inhibited RANKL-induced osteoclast formation without cytotoxicity. In particular, decursin maintains the characteristics of macrophages by blocking osteoclast differentiation by RANKL. Furthermore, the RANKL-stimulated bone resorption was diminished by decursin. Mechanistically, decursin blocked the RANKL-triggered ERK mitogen-activated protein kinases (MAPK) phosphorylation, which results in suppression of c-Fos and the nuclear factor of activated T cells (NFATc1) expression. In accordance with the in vitro study, decursin reduced lipopolysaccharide (LPS)- or ovariectomy (OVX)-induced bone loss in vivo. Therefore, decursin exerted an inhibitory effect on osteoclast formation and bone loss in vitro and in vivo. Decursin could be useful for the treatment of bone diseases associated with excessive bone resorption.
authors.affiliation: College of Pharmacy, Sookmyung Women's University, Cheongpa-ro 47-gil, Yongsan-gu, Seoul 04310, Republic of Korea.
authors.forename: Xin
authors.initials: X
authors.lastname: Wang
authors.affiliation: College of Pharmacy, Sookmyung Women's University, Cheongpa-ro 47-gil, Yongsan-gu, Seoul 04310, Republic of Korea.
authors.forename: Ting
authors.initials: T
authors.lastname: Zheng
authors.affiliation: College of Pharmacy, Sookmyung Women's University, Cheongpa-ro 47-gil, Yongsan-gu, Seoul 04310, Republic of Korea.
authors.forename: Ju-Hee
authors.initials: JH
authors.lastname: Kang
authors.affiliation: College of Pharmacy, Sookmyung Women's University, Cheongpa-ro 47-gil, Yongsan-gu, Seoul 04310, Republic of Korea; Research Center for Cell Fate Control, Sookmyung Women's University, Cheongpa-ro 47-gil, Yongsan-gu, Seoul 04310, Republic of Korea.
authors.forename: Hua
authors.initials: H
authors.lastname: Li
authors.affiliation: College of Pharmacy, Sookmyung Women's University, Cheongpa-ro 47-gil, Yongsan-gu, Seoul 04310, Republic of Korea; Research Center for Cell Fate Control, Sookmyung Women's University, Cheongpa-ro 47-gil, Yongsan-gu, Seoul 04310, Republic of Korea.
authors.forename: Hyewon
authors.initials: H
authors.lastname: Cho
authors.affiliation: College of Pharmacy, Sookmyung Women's University, Cheongpa-ro 47-gil, Yongsan-gu, Seoul 04310, Republic of Korea; Research Center for Cell Fate Control, Sookmyung Women's University, Cheongpa-ro 47-gil, Yongsan-gu, Seoul 04310, Republic of Korea.
authors.forename: Raok
authors.initials: R
authors.lastname: Jeon
authors.affiliation: College of Pharmacy, Sookmyung Women's University, Cheongpa-ro 47-gil, Yongsan-gu, Seoul 04310, Republic of Korea; Research Center for Cell Fate Control, Sookmyung Women's University, Cheongpa-ro 47-gil, Yongsan-gu, Seoul 04310, Republic of Korea. Electronic address: ryuha@sookmyung.ac.kr.
authors.forename: Jae-Ha
authors.initials: JH
authors.lastname: Ryu
authors.affiliation: College of Pharmacy, Sookmyung Women's University, Cheongpa-ro 47-gil, Yongsan-gu, Seoul 04310, Republic of Korea. Electronic address: myim@sm.ac.kr.
authors.forename: Mijung
authors.initials: M
authors.lastname: Yim
mesh_terms: D029969:Angelica / Q000737:chemistry*; D000818:Animals; D001578:Benzopyrans / Q000302:isolation & purification / Q000494:pharmacology*; D001862:Bone Resorption / Q000139:chemically induced* / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D002087:Butyrates / Q000302:isolation & purification / Q000494:pharmacology*; D015536:Down-Regulation / Q000187:drug effects; D005260:Female; D008070:Lipopolysaccharides / Q000494:pharmacology; D020935:MAP Kinase Signaling System / Q000187:drug effects; D008264:Macrophages / Q000187:drug effects; D051379:Mice; D008813:Mice, Inbred ICR; D050778:NFATC Transcription Factors / Q000378:metabolism; D010010:Osteoclasts / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology*; D010052:Ovariectomy / Q000009:adverse effects; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D053245:RANK Ligand / Q000494:pharmacology*
chemical_list: D001578:Benzopyrans; D002087:Butyrates; D008070:Lipopolysaccharides; D050778:NFATC Transcription Factors; D016760:Proto-Oncogene Proteins c-fos; D053245:RANK Ligand; C101278:decursin
keywords: Angelica gigas; Bone loss; Decursin; Decursin (PubChem CID: 442126); NFATc1; Osteoclast; c-Fos