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

Abstract

The signal transduction mechanism for aluminum (Al 3+ )-induced stimulation of bone formation and its crosstalk with the prostaglandin E 2 (PGE 2 ) signaling pathway were studied in calvarial osteoblasts from 25-week-old rats (MOB) and those from 90-week-old rats (AOB). Alkaline phosphatase activity, the rate of [ 3 H]proline incorporation into collagenase-digestible proteins, the total area and number of mineralized bone nodules (BN) and the content of calcium in BN, which are the markers for differentiation of osteoblasts, were dose-dependently stimulated by the treatment with Al 3+ at a concentration range of 10 ] i ) in 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-PGE 2 , a selective agonist for an EP 1 subtype of PGE 2 receptor (EP 1 ), 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 EP 1 . The levels of the differentiation markers obtained in the presence of the EP 1 agonist were increased by the addition of Al 3+ in the cultures of MOB and AOB, while Al 3+ increased the levels of IP 3 production and [Ca 2+ ] i in the presence of the EP 1 agonist only in the cultures of AOB. These results indicate a possibility that PI-PLC molecules stimulated by the signal through G i protein and those stimulated by the signal through EP 1 belong to the same pool and that the Al 3+ signal through G i 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-PGE 1 , a selective agonist for an EP 2 /EP 4 subtype of PGE 2 receptor (EP 2 /EP 4 ), 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 EP 2 /EP 4 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 EP 2 /EP 4 -mediated signal through the G i protein-coupled receptor.

The effect of surface pre‐reacted glass‐ionomer filler eluate on dental pulp cells and mineral deposition on dentin: In vitro study

“…Si ions exhibit antioxidant activity and enhance bone formation [31]. F ions stimulate osteoprogenitor cells [32] and Al ions trigger bone nodule formation [33], and the combination of F and Al ions has been reported to enhance the proliferation and differentiation of human pulp cells without toxicity [18]. Meanwhile, there are various reports on the toxicity of these ions, especially F [34].…”

Prostaglandin E2 Enhances B-Type Natriuretic Peptide Receptor Expression in Calvarial Osteoblasts through EP1 Subtype of Prostaglandin E2 Receptor

“…20) The binding of PGE 2 to the EP2 or EP4 receptor leads to the activation of adenylate cyclase to produce cAMP. On the other hand, the binding of PGE 2 to the EP1 receptor leads to the elevation of intracellular Ca 2+ level through the activation of phosphatidylinositol-specific phospholipase C. The Ca 2+ mobilization activates a phosphodiesterase that blocks the signaling through EP2 or EP4 by degrading cAMP.…”

“…20) We next examined the agedependent changes in the basal expression levels of EP1 and NPR-B using calvarial osteoblasts from rats of various ages (Fig. 4).…”