title: In Vitro and In Vivo Osteogenic Activity of Largazole.
abstract: Due to their capability of modifying chromatin structure and thereby regulating gene transcription, histone deacetylases (HDACs) have been reported to play important roles in osteogenesis and considered a promising potential therapeutic target for bone diseases, including osteoporosis. We showed that the novel marine-derived HDAC inhibitor largazole exhibits in vitro and in vivo osteogenic activity. Largazole significantly induced the expression of ALP and OPN. The osteogenic activity of largazole was mediated through the increased expression of Runx2 and BMPs. Importantly, largazole showed in vivo bone-forming efficacy in the mouse calvarial bone formation assay and the rabbit calvarial bone fracture healing model. The dual action of largazole to stimulate bone formation and inhibit bone resorption would be a useful feature in drug development for bone-related disorders.
authors.affiliation: Laboratory of Chemical Genomics, Korea Research Institute of Chemical Technology, Daejeon 305-600, Korea.
authors.forename: Su-Ui
authors.initials: SU
authors.lastname: Lee
authors.forename: Han Bok
authors.initials: HB
authors.lastname: Kwak
authors.forename: Sung-Hee
authors.initials: SH
authors.lastname: Pi
authors.forename: Hyung-Keun
authors.initials: HK
authors.lastname: You
authors.forename: Seong Rim
authors.initials: SR
authors.lastname: Byeon
authors.forename: Yongcheng
authors.initials: Y
authors.lastname: Ying
authors.forename: Hendrik
authors.initials: H
authors.lastname: Luesch
authors.forename: Jiyong
authors.initials: J
authors.lastname: Hong
authors.forename: Seong Hwan
authors.initials: SH
authors.lastname: Kim