title: Glycyrrhizae Radix Inhibits Osteoclast Differentiation by Inhibiting c-Fos-Dependent NFATc1 Expression.
abstract: Osteoporosis results from imbalance between new bone formation and bone resorption leading to bone loss and is especially troublesome for postmenopausal women who suffer from estrogen deficiency. The ability of new therapeutic agents to treat this bone disease with minimal side effects has been extensively reported on and is continuously being sought out by researchers in this field. Thus, the purpose of this study was to investigate a natural herb that was already being used as a new treatment for osteoporosis. Here we found that water extract of Glycyrrhizae radix (GR) inhibits receptor activator of nuclear factor-[Formula: see text]B ligand (RANKL)-induced osteoclast differentiation in a dose-dependent manner without causing cytotoxicity. The mRNA expression of c-Fos, nuclear factor of activated T cells cytoplasmic 1 (NFATc1), tartrate-resistant acid phosphatase (TRAP), and osteoclast-associated receptor (OSCAR) was considerably inhibited by GR treatment. GR inhibited RANKL-mediated c-Fos and NFATc1 expression in a dose-dependent manner. GR inhibited the degradation of I-[Formula: see text]B in RANKL-stimulated BMMs. However, GR-mediated inhibition of osteoclast differentiation and osteoclast-specific gene expression, including NFATc1, was reversed by ectopic expression of c-Fos. Also, GR significantly inhibited osteoclast formation in mouse calvariae in the presence of IL-1 and prostaglandin E2 (PGE2). Taken together, these results suggest that GR inhibited osteoclast differentiation, raising the possibility that GR may serve as a useful drug for osteoporosis.
authors.affiliation: * Department of Herbal Medicine, College of Pharmacy, Wonkwang University, 460 Iksan-daero, Iksan, Jeonbuk, Korea.
authors.forename: Tae Won
authors.initials: TW
authors.lastname: Rho
authors.affiliation: * Department of Herbal Medicine, College of Pharmacy, Wonkwang University, 460 Iksan-daero, Iksan, Jeonbuk, Korea.
authors.forename: Seo Young
authors.initials: SY
authors.lastname: Lee
authors.affiliation: * Department of Herbal Medicine, College of Pharmacy, Wonkwang University, 460 Iksan-daero, Iksan, Jeonbuk, Korea.|† Department of Herbal Resources, Professional Graduate School of Oriental Medicine, BK21 Plus Team, Wonkwang University, 460 Iksan-daero, Iksan, Jeonbuk, Korea.
authors.forename: Sang-Yong
authors.initials: SY
authors.lastname: Han
authors.affiliation: * Department of Herbal Medicine, College of Pharmacy, Wonkwang University, 460 Iksan-daero, Iksan, Jeonbuk, Korea.|† Department of Herbal Resources, Professional Graduate School of Oriental Medicine, BK21 Plus Team, Wonkwang University, 460 Iksan-daero, Iksan, Jeonbuk, Korea.
authors.forename: Ji Hoon
authors.initials: JH
authors.lastname: Kim
authors.affiliation: † Department of Herbal Resources, Professional Graduate School of Oriental Medicine, BK21 Plus Team, Wonkwang University, 460 Iksan-daero, Iksan, Jeonbuk, Korea.
authors.forename: Kyung-Hee
authors.initials: KH
authors.lastname: Lee
authors.affiliation: § Herbal Medicine Resources Group, Korea Institute, 1672 Yuseong-daero, Daejon, Korea.
authors.forename: Dong-Seon
authors.initials: DS
authors.lastname: Kim
authors.affiliation: † Department of Herbal Resources, Professional Graduate School of Oriental Medicine, BK21 Plus Team, Wonkwang University, 460 Iksan-daero, Iksan, Jeonbuk, Korea.
authors.forename: Han Bok
authors.initials: HB
authors.lastname: Kwak
authors.affiliation: * Department of Herbal Medicine, College of Pharmacy, Wonkwang University, 460 Iksan-daero, Iksan, Jeonbuk, Korea.|‡ Wonkwang Oriental Medicines Research Institute, Wonkwang University, 460 Iksan-daero, Iksan, Jeonbuk, Korea.
authors.forename: Yun-Kyung
authors.initials: YK
authors.lastname: Kim
mesh_terms: D029023:Acorus; D000818:Animals; D001854:Bone Marrow Cells; D002454:Cell Differentiation / Q000187:drug effects*; D002478:Cells, Cultured; D003864:Depression, Chemical; D004305:Dose-Response Relationship, Drug; D015870:Gene Expression / Q000187:drug effects*; D006035:Glycyrrhiza; D008297:Male; D008813:Mice, Inbred ICR; D058990:Molecular Targeted Therapy; D050778:NFATC Transcription Factors / Q000235:genetics* / Q000378:metabolism; D010010:Osteoclasts / Q000166:cytology*; D010024:Osteoporosis / Q000188:drug therapy; D010936:Plant Extracts / Q000494:pharmacology* / Q000627:therapeutic use; D016760:Proto-Oncogene Proteins c-fos / Q000502:physiology*
chemical_list: D050778:NFATC Transcription Factors; C494005:Nfatc1 protein, mouse; D010936:Plant Extracts; D016760:Proto-Oncogene Proteins c-fos
keywords: Glycyrrhizae Radix; Osteoclast Differentiation; Osteoporosis; c-Fos-Dependent NFATc1 Expression