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Biochem Biophys Res Commun. 1998 Nov 27;252(3):697-702.

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

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Department of Oral Pathology, Department of Biochemistry, School of Dentistry, Showa University, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo, 142-8555, Japan.


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.

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