Inhibition of osteoclastogenesis by a phosphodiesterase 4 inhibitor XT-611 through synergistic action with endogenous prostaglandin E2

摘要: Abstract We examined the effect of a phosphodiesterase 4 (PDE4) inhibitor, 3,4-dipropyl-4,5,7,8-tetrahydro-3 H -imidazo[1,2- i ]-purin-5-one (XT-611) on osteoclast formation in three different mouse bone-marrow cell (BMC) culture systems. confirmed that selective inhibitors PDE4, including XT-611, among several PDE decreased BMC system. XT-611 also inhibited co-culture stromal line ST2 and adherent cell-depleted (ACD)-BMCs. However, it did not inhibit osteoclastogenesis ACD-BMCs alone presence macrophage-colony stimulating factor (M-CSF) soluble receptor activator NF-κB ligand (sRANKL). significantly increased prostaglandin E 2 (PGE ) production from cells and, combination with PGE , synergistically cAMP concentration progenitors. In system, influence expression RANKL, osteoprotegerin RANK mRNAs. By combined treatment ACD-BMCs, multinucleation was clearly decrease calcitonin mRNA, while c-fms (an M-CSF receptor) mRNAs unchanged. These results indicate PDE4 inhibitor inhibits by acting progenitors secreted cells, but influencing cell-to-cell interaction between