PGE2 induces the transition from non-adherent to adherent bone marrow mesenchymal precursor cells via a cAMP/EP2-mediated mechanism.
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 PGE2, 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 PGE2. On the other hand, phorbol 12-myristate 13-acetate (PMA), an activator of protein kinase C, and sulprostone, an agonist for the PGE2 receptor EP1/EP3 subtypes, had no effect. The phosphodiesterase inhibitor, isobutylmethylxanthine (IBMX), had a synergistic effect in combination with PGE2, whereas neomycin, an inhibitor of inositol phosphate activity, had no effect, and LiC1, an inhibitor of inositol triphosphate metabolism, had an inhibitory effect on the PGE2-induced transition. Consistent with this, the addition of PGE2 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 EP2-PGE2 receptor subtype via an increase in intracellular cAMP synthesis.
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D000818:Animals; D001853:Bone Marrow / Q000187:drug effects* / Q000502:physiology; D001854:Bone Marrow Cells; D003994:Bucladesine / Q000494:pharmacology; D002448:Cell Adhesion / Q000187:drug effects*; D002478:Cells, Cultured; D005576:Colforsin / Q000494:pharmacology; D003114:Colony-Forming Units Assay; D000242:Cyclic AMP / Q000378:metabolism*; D003907:Dexamethasone / Q000494:pharmacology; D015232:Dinoprostone / Q000031:analogs & derivatives / Q000494:pharmacology*; D005260:Female; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D007700:Kinetics; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D011494:Protein Kinases / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D018078:Receptors, Prostaglandin E / Q000819:agonists / Q000502:physiology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D010726:Phosphodiesterase Inhibitors; D018078:Receptors, Prostaglandin E; D005576:Colforsin; C016767:sulprostone; D003994:Bucladesine; D003907:Dexamethasone; D000242:Cyclic AMP; D011494:Protein Kinases; D015232:Dinoprostone; D013755:Tetradecanoylphorbol Acetate; D015056:1-Methyl-3-isobutylxanthine