@entity1356 induces XXXX formation in isolated @entity1 osteoblasts: a signalling mechanism that is not related to enhanced @entity3009 formation.

@entity1 @entity1356 @entity1421 @entity3009 @entity1919 @entity1192 @entity10995 @entity460 @entity3365 @entity3352 @entity1928
@entity1192 ( @entity1192 ) is a potent stimulator of bone resorption. Induction of osteoclastic bone resorption by various endocrine or paracrine factors is mediated via the osteoblasts. We have therefore investigated the effects of @entity1356 on cell signalling in isolated @entity1 osteoblasts. Special interest was focused on @entity3009 synthesis, since @entity3352 , an inhibitor of @entity3009 synthesis, partly inhibits @entity1192 -induced bone resorption. @entity1356 , at and above 0.3 pM, dose dependently stimulated @entity1421 formation in isolated @entity1 osteoblasts, with half maximal stimulation, EC50, at 3 pM. Treatment with the @entity460 ionophore @entity3365 (1 microM), or with @entity1928 (30 microM), also stimulated @entity1421 formation in @entity1 osteoblasts. The time-course for @entity1356 -induced @entity1421 formation was similar to that of @entity1928 , with a significant increase in the formation of @entity1421 seen after 1 h. In contrast, @entity3365 -induced @entity1421 formation was seen within minutes. @entity1356 stimulated the accumulation of @entity1919 in isolated @entity1 osteoblasts incubated for 15 min. This increase in @entity1919 formation was not secondary to @entity1421 formation since it was not blocked by the addition of @entity3352 (1 microM). Pretreatment with the phosphodiesterase inhibitor IBMX did not augment @entity1356 -induced @entity1421 formation, nor did the protein kinase A inhibitor @entity10995 inhibit @entity1356 -induced @entity1421 formation, suggesting that @entity1919 does not mediate the stimulatory effect of @entity1192 on @entity1421 formation. We conclude that @entity1356 enhances the formation of @entity1919 as well as @entity1421 in primary cultures of isolated @entity1 osteoblasts. The @entity1356 -induced @entity1919 formation is, however, not related to the enhanced @entity3009 formation. The findings implicate that both @entity1919 - and @entity1421 -formation in osteoblasts might be involved as independent mediators of @entity1356 -induced bone resorption.
