Potential role of Cbfa1, an essential transcriptional factor for osteoblast differentiation, in osteoclastogenesis:: Regulation of mRNA expression of osteoclast differentiation factor (ODF)

The role of Gbfa1 (core binding factor alpha 1), 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(+/+) Cbfa(1+/-) and Cbfa1(-/-)) and normal spleen cells generated TRAP-positive multinucleated osteoclast-like cells (OCLs) in response to 1 alpha,25-dihydroxyvitamin D-3 [1 alpha,25(OH)(2)D-3] and dexamethasone, but the number and bone-resorbing activity of OGLs formed in coculture with Cbfa1(-/-) calvarial cells were significantly decreased in comparison with those formed in cocultures with Cbfa1(+/+) or Cbfa1(+/-) calvarial cells. The expression of osteoclast differentiation factor/osteoprotegerin ligand (ODF/OPGL) mRNA was increased by the treatment with 1 alpha,25(OH)(2)D-3 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 [1 alpha,25(OH)(2)D-3] 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 Gbfa1 is somehow involved in osteoclastogenesis through regulation of ODF/OPGL. (C) 1998 Academic Press.