A prostanoid receptor EP4 agonist enhances ectopic bone formation induced by recombinant human bone morphogenetic protein-2.
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.
Sasaoka
Ryuichi
R
Department of Orthopaedic Surgery, Osaka City University Graduate School of Medicine, 1-4-3 Asahi-machi, Abeno-ku, Osaka 545-8585, Japan.
Terai
Hidetomi
H
Toyoda
Hiromitsu
H
Imai
Yuuki
Y
Sugama
Ryo
R
Takaoka
Kunio
K
D020341:Absorbable Implants; D015502:Absorptiometry, Photon / Q000379:methods; D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D015519:Bone Density / Q000187:drug effects; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins / Q000235:genetics / Q000494:pharmacology*; D001842:Bone and Bones / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000648:ultrastructure; D003094:Collagen; D004305:Dose-Response Relationship, Drug; D004337:Drug Carriers; D006537:Heptanoates / Q000494:pharmacology*; D006801:Humans; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D015675:Osteocalcin / Q000097:blood; D010012:Osteogenesis / Q000187:drug effects*; D018078:Receptors, Prostaglandin E / Q000819:agonists*; D058309:Receptors, Prostaglandin E, EP4 Subtype; D011994:Recombinant Proteins / Q000235:genetics / Q000494:pharmacology; D016212:Transforming Growth Factor beta
C525718:BMP2 protein, human; C525719:Bmp2 protein, mouse; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins; D004337:Drug Carriers; D006537:Heptanoates; C487764:ONO4819; C545650:PTGER4 protein, human; C545651:Ptger4 protein, mouse; D018078:Receptors, Prostaglandin E; D058309:Receptors, Prostaglandin E, EP4 Subtype; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta; C499469:recombinant human bone morphogenetic protein-2; D015675:Osteocalcin; D003094:Collagen; D000469:Alkaline Phosphatase