title: Regulation of osteoclastogenesis by antisense oligodeoxynucleotides specific to zinc finger nuclear transcription factors Egr-1 and WT1 in rat bone marrow culture system.
abstract: Differentiation of osteoclasts is defined by the transcription factors expressed in response to bone microenvironments. In this work, we examined the effects of an expressional blockage of Egr-1 and/or WT1 on the differentiation of osteoclasts using specific antisense oligodeoxynucleotides (ODN). In a culture system forming preosteoclast-like cells (POC) from rat bone marrow cells depleted of marrow stromal cells, POC formation was markedly stimulated by the addition of Egr-1 antisense ODN compared to that in cultures in which sense ODN was added, whereas Egr-1 antisense ODN inhibited the formation of macrophage-like cells. The formation of multinucleated osteoclast-like cells was also stimulated by the addition of Egr-1 antisense ODN in whole bone marrow cultures. In contrast, WT1 antisense ODN did not affect POC formation induced by the treatment with Egr-1 antisense ODN; however, WT1 antisense ODN dramatically suppressed the formation of osteoclast-like multinucleated cells induced by the blockage of Egr-1 expression using Egr-1 antisense ODN. These data suggest that Egr-1 acts as the suppressor, not as the inducer, in osteoclastogenesis. The findings also suggested that WT1 could be involved in the multinucleation step of osteoclastogenesis, at least when Egr-1 expression was blocked.
authors.affiliation: Second Department of Oral Anatomy, Faculty of Dentistry, Kyushu University, Fukuoka, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Kukita
authors.forename: A
authors.initials: A
authors.lastname: Kukita
authors.forename: H
authors.initials: H
authors.lastname: Harada
authors.forename: T
authors.initials: T
authors.lastname: Iijima
mesh_terms: D000818:Animals; D001483:Base Sequence; D001853:Bone Marrow / Q000737:chemistry / Q000187:drug effects; D001854:Bone Marrow Cells; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D004247:DNA / Q000032:analysis / Q000737:chemistry / Q000235:genetics; D004268:DNA-Binding Proteins / Q000737:chemistry* / Q000235:genetics / Q000502:physiology; D051766:Early Growth Response Protein 1; D017874:Immediate-Early Proteins; D008297:Male; D016376:Oligonucleotides, Antisense / Q000737:chemistry / Q000235:genetics / Q000494:pharmacology*; D010010:Osteoclasts / Q000737:chemistry / Q000166:cytology* / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D015682:Retroviridae Proteins, Oncogenic / Q000737:chemistry* / Q000235:genetics / Q000502:physiology; D013234:Stem Cells / Q000737:chemistry / Q000166:cytology / Q000187:drug effects; D014157:Transcription Factors / Q000737:chemistry* / Q000235:genetics / Q000502:physiology; D025721:WT1 Proteins; D016335:Zinc Fingers / Q000235:genetics*
chemical_list: D004268:DNA-Binding Proteins; D051766:Early Growth Response Protein 1; C486110:Egr1 protein, rat; D017874:Immediate-Early Proteins; D016376:Oligonucleotides, Antisense; D015682:Retroviridae Proteins, Oncogenic; D014157:Transcription Factors; D025721:WT1 Proteins; D004247:DNA