title: Kruppel-like factor 4 expression in osteoblasts represses osteoblast-dependent osteoclast maturation.
abstract: Kruppel-like factor 4 (KLF4) is a zinc-finger-type transcription factor with a restricted expression pattern during skeletal development. We have previously shown that KLF4 represses osteoblast mineralization concomitant with a down-regulation in the expression of a number of osteoblastic genes, both in vivo and in vitro. In addition to the cell-autonomous effects of KLF4 in osteoblasts, transgenic osteoblastic-KLF4 mice show severe defects in osteoclast maturation. Wild-type bone-marrow-derived macrophages co-cultured with KLF4-expressing osteoblasts exhibit reduced formation of multinuclear osteoclasts as compared with control cultures overexpressing green fluorescent protein. Significantly, the transduction of Runx2, a master regulator of osteoblastogenesis, together with KLF4 into osteoblasts restores the reduction in osteoclastogenesis induced by KLF4 alone. Various extracellular matrix molecules are down-regulated by KLF4 overexpression but this down-regulation can be partially restored by the co-transduction of Runx2. These results suggest that osteoblastic-KLF4 affects osteoclast maturation by regulating cell-matrix interactions and reinforce the importance of the regional down-regulation of KLF4 expression in the subset of osteoblasts for normal skeletal modeling and remodeling.
authors.affiliation: Department of Oral Anatomy and Developmental Biology, Osaka University Graduate School of Dentistry, 1-8 Yamadaoka, Suita, Osaka, 565-0871, Japan.
authors.forename: Junji
authors.initials: J
authors.lastname: Fujikawa
authors.forename: Mariko
authors.initials: M
authors.lastname: Tanaka
authors.forename: Shousaku
authors.initials: S
authors.lastname: Itoh
authors.forename: Toshiya
authors.initials: T
authors.lastname: Fukushi
authors.forename: Kojiro
authors.initials: K
authors.lastname: Kurisu
authors.forename: Yuto
authors.initials: Y
authors.lastname: Takeuchi
authors.forename: Ichijiro
authors.initials: I
authors.lastname: Morisaki
authors.forename: Satoshi
authors.initials: S
authors.lastname: Wakisaka
authors.forename: Makoto
authors.initials: M
authors.lastname: Abe
mesh_terms: D000818:Animals; D016723:Bone Remodeling / Q000502:physiology*; D050659:Core Binding Factor Alpha 1 Subunit / Q000096:biosynthesis / Q000235:genetics; D015536:Down-Regulation / Q000502:physiology*; D005109:Extracellular Matrix / Q000235:genetics / Q000378:metabolism*; D000090062:Kruppel-Like Factor 4; D051741:Kruppel-Like Transcription Factors / Q000096:biosynthesis* / Q000235:genetics; D051379:Mice; D008822:Mice, Transgenic; D010006:Osteoblasts / Q000166:cytology / Q000378:metabolism*; D010010:Osteoclasts / Q000166:cytology / Q000378:metabolism*
chemical_list: D050659:Core Binding Factor Alpha 1 Subunit; C000715468:Klf4 protein, mouse; D000090062:Kruppel-Like Factor 4; D051741:Kruppel-Like Transcription Factors; C493716:Runx2 protein, mouse