PROSTAGLANDIN E(2) STIMULATES OSTEOCLAST-LIKE CELL-FORMATION AND BONE-RESORBING ACTIVITY VIA OSTEOBLASTS - ROLE OF CAMP-DEPENDENT PROTEIN-KINASE

Prostaglandin E(2) (PGE(2)) is an important local regulator in bone, T he present study was performed to investigate the effect of PGE(2) on osteoclast-like cell formation acid bone-resorbing activity of mature osteoclasts in the presence or absence of osteoblasts. PGE(2) (10(-8) to 10(-6) M) significantly stimulated osteoclast-like cell formation i n osteoblast-containing mouse bone cell cultures, although it did not affect osteoclast-like cell formation from hemopoietic blast cells sup ported by granulocyte-macrophage colony-stimulating factor in osteobla st-free mouse spleen cell cultures. The conditioned medium from osteob lastic UMR-106 cells pretreated with PGE(2) (10(-8) and 10(-6) hi) sig nificantly stimulated osteoclast-like cell formation from hemopoietic blast cells, PGE(2) also significantly stimulated the bone-resorbing a ctivity of mature osteoclasts in osteoblast-containing mouse bone cell cultures, In contrast, PGE(2) significantly inhibited the bone-resorb ing activity and osteopontin mRNA expression in isolated rabbit osteoc lasts, Rp-cAMPS, a direct protein kinase (PKA) antagonist, significant ly inhibited PGE(2)-stimulated osteoclast-like cell formation and the bone-resorbing activity of mature osteoclasts, although protein kinase C inhibitors, dantrolene (an inhibitor of calcium release from the in tracellular calcium pool) and voltage-dependent calcium channel blocke rs did not affect PGE(2)-stimulated osteoclast-like cell formation, In conclusion, PGE(2) stimulated osteoclast-like cell formation and bone -resorbing activity in mouse bone cell cultures presumably through ost eoblasts. The activation of PKA is linked to PGE(2)-stimulated osteocl ast-like cell formation and bone-resorbing activity.