Abstract
We have developed a mouse marrow culture system in which multinucleated osteoclast (OC) -like cells are formed within 8 days. Using this culture system, we examined the effect of prostaglandins (PGs), potent bone-resorting agents, on OC-like cell formation. Four PGs (PGE1 and PGE2 at 10-8-10-5 M, 6-keto-PGF1αat 10-5M, and PGF2αat 10-6-10-5M) significantly stimulated the formation of OC-like cells. The potency of the PGs in inducing OC-like cell forma-tion was well correlated with the potency in increasing the production of cyclic adenosine 3', 5'-monophosphate (cAMP) in bone marrow cells. Addition of dibutyryl-CAMP also induced OC-like cell formation. Moreover, isobutylmethylxanthine (IBMX), a potent inhibitor of phosphodiesterase, potentiated the OC-like cell formation induced by PGE2. Calcitonin induced cAMP production in cultures treated with PGE2, but not in cultures with vehicle. When bone marrow mononuclear cells were cultured on dentine slices in the presence of PGE2, multinucleated OC-like cells were similarly formed and they resorbed calcified tissues.
These results suggest that PGs stimulate resorption of calcified tissues by promoting osteoclast formation. The activity of PGs in inducing OC-like cell formation is considered mediated by a mechanism involving cAMP.
