RETINOIC ACID INDUCES OSTEOCLAST-LIKE CELL-FORMATION BY DIRECTLY ACTING ON HEMATOPOIETIC BLAST CELLS AND STIMULATES OSTEOPONTIN MESSENGER-RNA 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 osteoc last-like cell formation in the presence or absence of osteoblasts and to study whether RA would affect osteopontin mRNA expression in isola ted rabbit osteoclasts. RA (10(-8) and 10(-6) M) significantly stimula ted the formation of osteoclast-like cell in osteoblast-containing mou se bone cell cultures. Also, RA caused a stimulation of osteoclast-lik e cell formation from hemopoietic blast cells supported by granulocyte macrophage-colony stimulating factor (GM-CSF) in mouse spleen cell cu ltures. However, RA did not affect blast cell number in these cultures and significantly inhibited GMCSF-stimulated proliferation of hemopoi etic 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 rab bit osteoclasts. The present study demonstrated for the first time tha t RA stimulated osteoclast-like cell formation, presumably through dir ectly acting on the hemopoietic blast cells, and that RA stimulated os teopontin mRNA expression in isolated rabbit osteoclasts.