PDE 저해제에 의한 PGE2의 파골세포 분화 유도 증강효과

The Stimulatory Effect of PDE Inhibitor on PGE2-Induced Osteoclastogenesis

To determine the regulatory roles of phosphodiestrase(PDE) inhibitors on PGE2-induced osteoclastogenesis, we investigated the effect of PDE inhibitors on osteoclast formation in the presence of PGE2. Among PDE isozyme specific inhibitors, milrinone, a selective PDE3 inhibitor, and rolipram, a specific PDE4 inhibitor, increased PGE2-induced osteoclastformation in cocultures of mouse bone marrow cells and osteoblast. To verify that whether the PDE3 and PDE4 inhibitors act indirectly on osteoblast, we measured the concentration of intracellular cAMP in osteoblast. Treatment of milrinone or rolipram increased PGE2-stimulated cAMP level in osteoblast. Furthermore, northen blot analysis revealed that the PDE3 and PDE4 inhibitors workers synergistically with PGE2 to increase the expression of TRANCE mRNA in osteoblasts. On the contrary, the PDE3 and PDE4 inhibitors did not argument the number of osteoclasts differentiated from bone marrow cells by PGE2. In conclusion, the stimulation of PGE2-induced osteoclast formation by the PDE3 and PDE4 inhibitors are attributable to their indirect effect on osteoblast, not to their direct effect in bone marrow-derived osteoclast precursors.