title: In vitro and in vivo osteogenic activity of licochalcone A.
abstract: We investigated the in vitro and in vivo osteogenic activity of licochalcone A. At low concentrations, licochalcone A stimulated the differentiation of mouse pre-osteoblastic MC3T3-E1 subclone 4 (MC4) cells and enhanced the bone morphogenetic protein (BMP)-2-induced stimulation of mouse bi-potential mesenchymal precursor C2C12 cells to commit to the osteoblast differentiation pathway. This osteogenic activity of licochalcone A was accompanied by the activation of extracellular-signal regulated kinase (ERK). The involvement of ERK was confirmed in a pharmacologic inhibition study. Additionally, noggin (a BMP antagonist) inhibited the osteogenic activity of licochalcone A in C2C12 cells. Licochalcone A also enhanced the BMP-2-stimulated expression of various BMP mRNAs. This suggested that the osteogenic action of licochalcone A in C2C12 cells could be dependent on BMP signaling and/or expression. We then tested the in vivo osteogenic activity of licochalcone A in two independent animal models. Licochalcone A accelerated the rate of skeletal development in zebrafish and enhanced woven bone formation over the periosteum of mouse calvarial bones. In summary, licochalcone A induced osteoblast differentiation with ERK activation in both MC4 and C2C12 cells and it exhibited in vivo osteogenic activity in zebrafish skeletal development and mouse calvarial bone formation. The dual action of licochalcone A in stimulating bone formation and inhibiting bone resorption, as described in a previous study, might be beneficial in treating bone-related disorders.
authors.affiliation: Laboratory of Chemical Genomics, Pharmacology Research Center, Korea Research Institute of Chemical Technology, P.O. Box 107, Yuseong-gu, Daejeon, 305-600, Republic of Korea.
authors.forename: Soon Nam
authors.initials: SN
authors.lastname: Kim
authors.forename: Su Jung
authors.initials: SJ
authors.lastname: Bae
authors.forename: Han Bok
authors.initials: HB
authors.lastname: Kwak
authors.forename: Yong Ki
authors.initials: YK
authors.lastname: Min
authors.forename: Seung-Hyun
authors.initials: SH
authors.lastname: Jung
authors.forename: Cheol-Hee
authors.initials: CH
authors.lastname: Kim
authors.forename: Seong Hwan
authors.initials: SH
authors.lastname: Kim
mesh_terms: D000818:Animals; D001846:Bone Development / Q000187:drug effects*; D055396:Bone Morphogenetic Protein 2; D002454:Cell Differentiation / Q000187:drug effects*; D002460:Cell Line; D047188:Chalcones / Q000494:pharmacology*; D051379:Mice; D008813:Mice, Inbred ICR; D010006:Osteoblasts / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D015027:Zebrafish
chemical_list: D055396:Bone Morphogenetic Protein 2; D047188:Chalcones; C070840:licochalcone A