title: Antisense targeting of TGF-beta1 augments BMP-induced upregulation of osteopontin, type I collagen and Cbfa1 in human Saos-2 cells.
abstract: Despite commonalities in signal transduction in osteoblasts from different species, the role of TGF-beta1 on bone formation remains elusive. In particular, the role of autocrine TGF-beta1 on human osteoblasts is largely unknown. Here we show the effect of TGF-beta1 knock-down on the proliferation and differentiation of osteoblasts induced by BMP2. Treatment with antisense TGF-beta1 moderately increased the rate of cell proliferation, which was completely reversed by the exogenous addition of TGF-beta1. Notably, TGF-beta1 blockade significantly enhanced BMP2-induced upregulation of mRNAs encoding osteopontin, type I collagen and Cbfa1, which was suppressed by exogenous TGF-beta1. Moreover, TGF-beta1 knock-down increased BMP2-induced phosphorylation of Smad1/5 as well as their nuclear import, which paralleled a reduction of inhibitory Smad6. These data suggest autocrine TGF-beta1 antagonizes BMP signaling through modulation of inducible Smad6 and the activity of BMP specific Smad1/5.
authors.affiliation: Department of Biochemistry, College of Natural Sciences, Kyungpook National University, Taegu 702-701, Korea. zshen2@wisc.edu <zshen2@wisc.edu>
authors.forename: Zhong-Jian
authors.initials: ZJ
authors.lastname: Shen
authors.forename: Sang Kook
authors.initials: SK
authors.lastname: Kim
authors.forename: Do Youn
authors.initials: DY
authors.lastname: Jun
authors.forename: Wan
authors.initials: W
authors.lastname: Park
authors.forename: Young Ho
authors.initials: YH
authors.lastname: Kim
authors.forename: James S
authors.initials: JS
authors.lastname: Malter
authors.forename: Byung Jo
authors.initials: BJ
authors.lastname: Moon
mesh_terms: D001483:Base Sequence; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins / Q000494:pharmacology*; D002454:Cell Differentiation; D002460:Cell Line; D049109:Cell Proliferation; D024042:Collagen Type I / Q000378:metabolism*; D050659:Core Binding Factor Alpha 1 Subunit / Q000378:metabolism*; D006801:Humans; D008969:Molecular Sequence Data; D020319:Oligodeoxyribonucleotides, Antisense / Q000235:genetics; D010006:Osteoblasts / Q000378:metabolism / Q000502:physiology; D053495:Osteopontin / Q000378:metabolism*; D010710:Phosphates / Q000737:chemistry; D010766:Phosphorylation; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000378:metabolism; D015398:Signal Transduction; D051785:Smad Proteins / Q000378:metabolism; D014162:Transfection; D016212:Transforming Growth Factor beta / Q000494:pharmacology*; D053773:Transforming Growth Factor beta1 / Q000235:genetics* / Q000378:metabolism; D015854:Up-Regulation
chemical_list: C525718:BMP2 protein, human; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins; D024042:Collagen Type I; D050659:Core Binding Factor Alpha 1 Subunit; D020319:Oligodeoxyribonucleotides, Antisense; D010710:Phosphates; D012333:RNA, Messenger; D051785:Smad Proteins; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D053495:Osteopontin; C083120:phosphorodithioic acid