title: EP4 agonist accelerates osteoinduction and degradation of beta-tricalcium phosphate by stimulating osteoclastogenesis.
abstract: Porous beta-tricalcium phosphate (TCP) has been known to have osteoinductive potential in ectopic site implantation in canine models without the use of osteoinductive substances or cell transplantation. Prostaglandin E2 receptors, particularly EP4, are known to play an important role in osteogenesis. EP4 agonists have been demonstrated to have positive effects on bone remodeling and bone morphogenic protein-induced ectopic bone formation in rodent models. We examined the efficiency of porousbeta-TCP-induced osteoinduction in beagles by the graded-release EP4 agonist, which was injected at their buttocks intramuscularly. Newly formed bone was observed on and after 3 weeks in the EP4 agonist-injected, while on and after 6 weeks in control groups, respectively. After that the bone resorption and the beta-TCP degradation was accelerated in EP4 agonist-injected group. Tartarate-resistant acid phosphatase-positive cells appeared in each group before bone formation, and the number of these cells reduced gradually; however, more multinucleated and larger cells appeared, particularly in the injected group. Injection of an EP4 agonist was proved to accelerate the osteoinduction and degradation of beta-TCP in canine model. Histological analysis revealed that the EP4 agonist stimulated osteoclastogenesis before bone formation.
authors.affiliation: Department of Orthopaedic Surgery, Kyoto University, Kawahara-cho, Shogoin, Sakyo-ku, Japan. nsu@kuhp.kyoto-u.ac.jp
authors.forename: Tomonori
authors.initials: T
authors.lastname: Nasu
authors.forename: Mitsuru
authors.initials: M
authors.lastname: Takemoto
authors.forename: Norihiro
authors.initials: N
authors.lastname: Akiyama
authors.forename: Shunsuke
authors.initials: S
authors.lastname: Fujibayashi
authors.forename: Masashi
authors.initials: M
authors.lastname: Neo
authors.forename: Takashi
authors.initials: T
authors.lastname: Nakamura
mesh_terms: D000135:Acid Phosphatase / Q000378:metabolism; D000818:Animals; D001842:Bone and Bones / Q000166:cytology / Q000201:enzymology; D002130:Calcium Phosphates / Q000378:metabolism*; D004285:Dogs; D005260:Female; D020007:Implants, Experimental; D007527:Isoenzymes / Q000378:metabolism; D010010:Osteoclasts / Q000166:cytology* / Q000187:drug effects*; D010012:Osteogenesis / Q000187:drug effects*; D016062:Porosity; D018078:Receptors, Prostaglandin E / Q000819:agonists*; D058309:Receptors, Prostaglandin E, EP4 Subtype; D012984:Software; D000071681:Tartrate-Resistant Acid Phosphatase
chemical_list: D002130:Calcium Phosphates; D007527:Isoenzymes; D018078:Receptors, Prostaglandin E; D058309:Receptors, Prostaglandin E, EP4 Subtype; C485817:beta-tricalcium phosphate; D000135:Acid Phosphatase; D000071681:Tartrate-Resistant Acid Phosphatase