Retinoic acid induces osteoclast-like cell formation by directly acting on hemopoietic blast cells and stimulates osteopontin mRNA expression in isolated osteoclasts.

Although retinoic acid (RA) has been considered to be a bone-resorbing agent both in vivo and in vitro, its mechanism remains still unclear. The present study was performed to examine the effect of RA on osteoclast-like cell formation in the presence or absence of osteoblasts and to study whether RA would affect osteopontin mRNA expression in isolated rabbit osteoclasts. RA (10(-8) and 10(-6) M) significantly stimulated the formation of osteoclast-like cell in osteoblast-containing mouse bone cell cultures. Also, RA caused a stimulation of osteoclast-like cell formation from hemopoietic blast cells supported by granulocyte macrophage-colony stimulating factor (GM-CSF) in mouse spleen cell cultures. However, RA did not affect blast cell number in these cultures and significantly inhibited GM-CSF-stimulated proliferation of hemopoietic blast cells. On the other hand, RA stimulated the bone-resorbing activity of mature osteoclasts in mouse bone cell cultures. Moreover, RA caused a stimulation of osteopontin mRNA expression in isolated rabbit osteoclasts. The present study demonstrated for the first time that RA stimulated osteoclast-like cell formation, presumably through directly acting on the hemopoietic blast cells, and that RA stimulated osteopontin mRNA expression in isolated rabbit osteoclasts.