Mechanism Underlying the Aluminum-Induced Stimulation of Bone Nodule Formation by Rat Calvarial Osteoblasts

Abstract

the cultures of MOB and AOB: these effects were not observed in the presence of PTX, indicating that the effects of Al 3+ are mediated through the activation of phosphatidylinositol-specific phospholipase C (PI-PLC). We have previously shown that 17-phenyl-ω-trinor-PGE2, a selective agonist for an EP1 subtype of PGE2 receptor (EP1), stimulates the differentiation markers in the cultures of MOB through the activation of PI-PLC, but not in those of AOB because of the lack of EP1. The levels of the differentiation markers obtained in the presence of the EP1 agonist were increased by the addition of Al 3+ in the cultures of MOB and AOB, while Al 3+ increased the levels of IP3 production and [Ca 2+ ]i in the presence of the EP1 agonist only in the cultures of AOB. These results indicate a possibility that PIPLC molecules stimulated by the signal through Gi protein and those stimulated by the signal through EP1 belong to the same pool and that the Al 3+ signal through Gi protein induces cell differentiation via a pathway(s) independent of PI-PLC in addition to that (those) dependent on the PI-PLC. We have also shown that 11-deoxy-PGE1, a selective agonist for an EP2/EP4 subtype of PGE2 receptor (EP2/EP4), inhibits cell differentiation in the cultures of both MOB and AOB. Al 3+ had no effect on the basal levels of cAMP production, but the levels induced by the EP2/EP4 agonist were dose‐dependently reduced by the treatment with Al 3+ at a concentration range of 10 ‐7 ‐10 ‐5 M. The inhibitory effect of Al 3+ on adenylyl cyclase was abolished by the pretreatment with PTX. These results indicate that Al 3+ suppresses adenylyl cyclase activity induced by the EP2/EP4-mediated signal through the Gi protein-coupled receptor.