Potential role of cbfa1, an essential transcriptional factor for osteoblast differentiation, in osteoclastogenesis: regulation of mRNA expression of osteoclast differentiation factor (ODF)

• Published in: Biochemical and biophysical research communications 1998-11, Vol.252 (3), p.697-702
• Main Authors: Gao, Y H, Shinki, T, Yuasa, T, Kataoka-Enomoto, H, Komori, T, Suda, T, Yamaguchi, A
• Format: Article
• Language: English
• Subjects: Animals; Bone Resorption - genetics; Carrier Proteins; Cell Differentiation; Cells, Cultured; Core Binding Factor Alpha 1 Subunit; Core Binding Factors; Cytokines - biosynthesis; Cytokines - genetics; Femur - metabolism; Macrophage Colony-Stimulating Factor - biosynthesis; Macrophage Colony-Stimulating Factor - genetics; Membrane Glycoproteins - biosynthesis; Membrane Glycoproteins - genetics; Mice; Mice, Knockout; Neoplasm Proteins; Osteoblasts - cytology; Osteoclasts - cytology; RANK Ligand; Receptor Activator of Nuclear Factor-kappa B; RNA, Messenger - biosynthesis; Tibia - metabolism; Transcription Factors - physiology
• ISSN: 0006-291X
• DOI: 10.1006/bbrc.1998.9643

The role of Cbfa1 (core binding factor alpha1), an essential transcriptional factor for osteoblast differentiation, in osteoclastogenesis was investigated in vitro and in vivo using Cbfa1-deficient calvarial cells and mice. Co-cultures of calvarial cells isolated from embryos with three different Cbfa1 genotypes (Cbfa1+/+, Cbfa1+/- and Cbfa1-/-) and normal spleen cells generated TRAP-positive multinucleated osteoclast-like cells (OCLs) in response to 1alpha,25-dihydroxyvitamin D3 [1alpha,25(OH)2D3] and dexamethasone, but the number and bone-resorbing activity of OCLs formed in co-culture with Cbfa1-/- calvarial cells were significantly decreased in comparison with those formed in co-cultures with Cbfa1+/+ or Cbfa1+/- calvarial cells. The expression of osteoclast differentiation factor/osteoprotegerin ligand (ODF/OPGL) mRNA was increased by the treatment with 1alpha, 25(OH)2D3 and dexamethasone in calvarial cells from Cbfa1+/+ and Cbfa1+/- mouse embryos, but not from Cbfa1-/- embryos. In contrast, the expression of osteoprotegerin/osteoclastogenesis inhibitory factor (OPG/OCIF) mRNA was inhibited by 1alpha,25(OH)2D3 and dexamethasone similarly in all three types of calvarial cells. ODF/OPGL and OPG/OCIF mRNAs were highly expressed in the tibia and femur of Cbfa1+/+ and Cbfa1+/- embryos. In the tibia and femur of Cbfa1-/- embryos, however, ODF/OPGL mRNA was undetectable and the expression of OPG/OCIF mRNA was also decreased compared with those in Cbfa1+/+ and Cbfa1+/- embryos. These results suggested that Cbfa1 is somehow involved in osteoclastogenesis through regulation of ODF/OPGL.