PGE 2 induces the transition from non-adherent to adherent bone marrow mesenchymal precursor cells via a cAMP/EP 2-mediated mechanism

Abstract

When mesenchymal precursor cells from bone marrow are cultured in the presence of dexamethasone, the existence of distinct non-adherent and adherent populations can be demonstrated. The addition of PGE 2, forskolin, or dibutyryl-cAMP can induce a transition from the former to the latter and this may be an important mechanism in the bone anabolic effects of PGE 2. On the other hand, phorbol 12-myristate 13-acetate (PMA), an activator of protein kinase C, and sulprostone, an agonist for the PGE 2 receptor EP 1/EP 3 subtypes, had no effect. The phosphodiesterase inhibitor, isobutylmethylxanthine (IBMX), had a synergistic effect in combination with PGE 2, whereas neomycin, an inhibitor of inositol phosphate activity, had no effect, and LiCl, an inhibitor of inositol triphosphate metabolism, had an inhibitory effect on the PGE 2-induced transition. Consistent with this, the addition of PGE 2 to non-adherent bone marrow cells caused a 100% increase in cAMP synthesis. These results suggest that the induction of the transition from non-adherent to adherent osteoblast precursor is mediated by the EP 2-PGE 2 receptor subtype via an increase in intracellular cAMP synthesis.