title: Expression of POEM, a positive regulator of osteoblast differentiation, is suppressed by TNF-α.
abstract: POEM, also known as nephronectin, is an extracellular matrix protein considered to be a positive regulator of osteoblast differentiation. In the present study, we found that tumor necrosis factor-α (TNF-α), a key regulator of bone matrix properties and composition that also inhibits terminal osteoblast differentiation, strongly inhibited POEM expression in the mouse osteoblastic cell line MC3T3-E1. TNF-α-induced down-regulation of POEM gene expression occurred in both time- and dose-dependent manners through the nuclear factor kappa B (NF-κB) pathway. In addition, expressions of marker genes in differentiated osteoblasts were down-regulated by TNF-α in a manner consistent with our findings for POEM, while over-expression of POEM recovered TNF-α-induced inhibition of osteoblast differentiation. These results suggest that TNF-α inhibits POEM expression through the NF-κB signaling pathway and down-regulation of POEM influences the inhibition of osteoblast differentiation by TNF-α.
authors.affiliation: Department of Biochemistry, School of Dentistry, Showa University, 1-5-8 Hatanodai, Shinagawa, Tokyo 142-8555, Japan.
authors.forename: Masayuki
authors.initials: M
authors.lastname: Tsukasaki
authors.forename: Atsushi
authors.initials: A
authors.lastname: Yamada
authors.forename: Dai
authors.initials: D
authors.lastname: Suzuki
authors.forename: Ryo
authors.initials: R
authors.lastname: Aizawa
authors.forename: Agasa
authors.initials: A
authors.lastname: Miyazono
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Miyamoto
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Suzawa
authors.forename: Masamichi
authors.initials: M
authors.lastname: Takami
authors.forename: Kentaro
authors.initials: K
authors.lastname: Yoshimura
authors.forename: Naoko
authors.initials: N
authors.lastname: Morimura
authors.forename: Matsuo
authors.initials: M
authors.lastname: Yamamoto
authors.forename: Ryutaro
authors.initials: R
authors.lastname: Kamijo
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects / Q000235:genetics*; D002460:Cell Line; D016326:Extracellular Matrix Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics*; D005786:Gene Expression Regulation; D006801:Humans; D051379:Mice; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism; D010006:Osteoblasts / Q000166:cytology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism* / Q000494:pharmacology
chemical_list: D016326:Extracellular Matrix Proteins; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; C432915:nephronectin