ono4819 and Body-Weight

The anabolic effects of prostaglandin E(2) on bone are effected through the activation of EP4, a G protein-coupled receptor. In the present study, we examined the effects of a prostanoid receptor-selective agonist (ONO-4819) in an experimental system of ectopic bone formation using recombinant human bone morphogenetic protein-2 (rhBMP-2). Collagen pellets containing rhBMP-2 were implanted onto the back muscles of mice and then treated with ONO-4819 administered every 8 h by subcutaneous injection. The ossicles elicited ectopically by rhBMP-2 in mice treated with 30 microg/kg ONO-4819 were significantly larger in size and had a higher bone mineral density and bone mineral content when compared to the controls. We also noted that the anabolic effect of ONO-4819 was seen only in the early phase of the rhBMP-2-induced bone-forming process. These experimental results indicate that the EP4 receptor agonist enhances the rhBMP-2-induced bone formation through a selective effect on early stage mesenchymal cells, which in turn may result in increased responsiveness of the host animals to rhBMP-2.

Topics: Absorbable Implants; Absorptiometry, Photon; Alkaline Phosphatase; Animals; Body Weight; Bone and Bones; Bone Density; Bone Morphogenetic Protein 2; Bone Morphogenetic Proteins; Collagen; Dose-Response Relationship, Drug; Drug Carriers; Heptanoates; Humans; Male; Mice; Mice, Inbred ICR; Osteocalcin; Osteogenesis; Receptors, Prostaglandin E; Receptors, Prostaglandin E, EP4 Subtype; Recombinant Proteins; Transforming Growth Factor beta