Morichika Takita
   Department   School of Medicine, School of Medicine
   Position   Assistant Professor
Article types Original article
Language English
Peer review Peer reviewed
Title Prostaglandin E receptor EP4 antagonist suppresses lipopolysaccharide-induced osteoclast formation and inflammatory bone loss.
Journal Formal name:Journal of Health Science
Abbreviation:J. Health Sci.
ISSN code:13449702/13475207
Domestic / ForeginDomestic
Publisher Pharmaceutical Society of JAPAN
Volume, Issue, Page 53(2),pp.234-239
Author and coauthor Matsumoto Chiho†, Takita Moirichika, Inada Masaki, Maruyama Takayuki, Miyaura Chisato*
Authorship 2nd author
Publication date 2007/04
Summary 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 PGE2-mediated EP4 signal is essential for LPS-induced osteoclast formation. Inflammatory bone diseases including periodontitis are known to be accompanied with the bone loss with increased osteoclastogenesis. To examine the role of EP4-medeiated PGE2 action in periodontitis, we examined the effects of EP4 antagonist on LPS-induced bone resorption using mouse alveolar bone. In organ culture of alveolar bone, LPS induced bone-resorbing activity and EP4 antagonist suppressed the LPS-induced bone resorption. In experimental model of periodontitis, LPS was injected into the lower gingiva and bone mineral density of alveolar bone was measured. LPS induced the loss of alveolar bone, which was recovered by the treatment of EP4 antagonist in vivo. Therefore, EP4 antagonist is a possible candidate for the therapy of inflammatory bone disease including periodontitis.