Prostaglandin E Receptor EP4 Antagonist Suppresses Lipopolysaccharide-Induced Osteoclast Formation and Inflammatory Bone Loss

• Published in: Journal of Health Science Vol. 53; no. 2; pp. 234 - 239
• Main Authors: Matsumoto, Chiho, Takita, Morichika, Inada, Masaki, Maruyama, Takayuki, Miyaura, Chisato
• Format: Journal Article
• Language: English; Japanese
• Published: The Pharmaceutical Society of Japan 01.01.2007; Pharmaceutical Society of Japan
• Subjects: bone resorption; EP4 receptor; inflammation; periodontitis; prostaglandin E
• ISSN: 1344-9702; 1347-5207
• DOI: 10.1248/jhs.53.234

Prostaglandin E2 (PGE2) is mainly produced by osteoblasts in bone tissue, and acts as a potent stimulator of bone resorption. In osteoblasts, PGE2 production was greatly stimulated by lipopolysaccharide (LPS) following the expression of cyclooxygenase (COX)-2 and membrane-bound PGE synthase (mPGES)-1 mRNA. In the coculture of mouse bone marrow cells and osteoblasts, LPS induced PGE production and osteoclast formation, and EP4 antagonist completely suppressed osteoclast formation, indicating that the PGE2-mediated EP4 signal is essential for LPS-induced osteoclast formation. Inflammatory bone diseases including periodontitis are known to be accompanied by bone loss with increased osteoclastogenesis. To examine the role of EP4-mediated PGE2 action in periodontitis, we examined the effects of EP4 antagonist on LPS-induced bone resorption using mouse alveolar bone. In an organ culture of alveolar bone, LPS-induced bone resorbing activity and EP4 antagonist suppressed this LPS-induced bone resorption. In an experimental model of periodontitis, LPS was injected into the lower gingiva, and the bone mineral density of alveolar bone was measured. LPS-induced the loss of alveolar bone, which was recovered by the treatment with EP4 antagonist in vivo. Therefore, EP4 antagonist is a possible candidate for the therapy of inflammatory bone disease including periodontitis.