PDE 저해제에 의한 PGE2의 파골세포 분화 유도 증강효과

Abstract

2-induced osteoclastogenesis,we investigated the effect of PDE inhibitors on osteoclast formation in the presence of PGE2. Among PDE isozyme specificinhibitors, milrinone, a selective PDE3 inhibitor, and rolipram, a specific PDE4 inhibitor, increased PGE2-induced osteoclastformation in cocultures of mouse bone marow cells and osteoblasts. To verify that whether the PDE3 and PDE4 inhibitorsact indirectly on osteoblasts, we measured the concentration of intracellular cAMP in osteoblasts. Treatment of milrinoneor rolipram increased PGE2-stimulated cAMP levels in osteoblasts. Furthermore, northern blot analysis revealed that thePDE3 and PDE4 inhibitors works synergistically with PGE2 to increase the expresion of TRANCE mRNA in osteoblasts.cells by PGE2. In conclusion, the stimulation of PGE2-induced osteoclast formation by the PDE3 and PDE4 inhibitors areattributable to their indirect effect on osteoblasts, not to their direct effect on bone marow-derived osteoclast precursors.Keywords . phosphodiesterase, osteoblast, osteoclast... .. .... .... (osteoblast). ....(osteoclast). ... .. .. ..... .... ....