HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Inada, M. Articles by Miyaura, C. Search for Related Content PubMed PubMed Citation Articles by Inada, M. Articles by Miyaura, C.

Membrane-Bound Prostaglandin E Synthase-1-Mediated Prostaglandin E₂ Production by Osteoblast Plays a Critical Role in Lipopolysaccharide-Induced Bone Loss Associated with Inflammation

Masaki Inada^*, Chiho Matsumoto^*, Satoshi Uematsu, Shizuo Akira and Chisato Miyaura^1,*

^* Department of Biotechnology and Life Science, Tokyo University of Agriculture and Technology, Tokyo, Japan; and Department of Host Defense, Research Institute for Microbial Diseases, Osaka University, Osaka, Japan

PGE₂ acts as a potent stimulator of bone resorption in several disorders including osteoarthritis and periodontitis. Three PGE synthases (PGES) were isolated for PGE₂ production, but which PGES has the major role in inflammatory bone resorption is still unclear. In this study, we examined the role of PGE₂ in LPS-induced bone resorption using membrane-bound PGES (mPGES)-1-deficient mice (mPges1^–/–). In osteoblasts from wild-type mice, PGE₂ production was greatly stimulated by LPS following the expression of cyclooxygenase 2 and mPGES-1 mRNA, whereas no PGE₂ production was found in osteoblasts from mPges1^–/–. LPS administration reduced the bone volume in wild-type femur that was associated with an increased number of osteoclasts. In mPges1^–/–, however, LPS-induced bone loss was reduced. We next examined whether mPGES-1 deficiency could alter the alveolar bone loss in LPS-induced experimental periodontitis. LPS was injected into the lower gingiva and bone mineral density of alveolar bone was measured. LPS induced the loss of alveolar bone in wild-type, but not in mPges1^–/– mice, suggesting an mPGES-1 deficiency resistant to LPS-induced periodontal bone resorption. To understand the pathway of LPS-induced PGE₂ production in osteoblast, we used C3H/HeJ mice with mutated tlr4. Osteoblasts from C3H/HeJ mice did not respond to LPS, and PGE₂ production was not altered at all. LPS-induced bone loss in the femur was also impaired in C3H/HeJ mice. Thus, LPS binds to TLR4 on osteoblasts that directly induce mPGES-1 expression for PGE₂ synthesis, leading to subsequent bone resorption. Therefore, mPGES-1 may provide a new target for the treatment of inflammatory bone disease.

This article has been cited by other articles:

				F. Kojima, M. Kapoor, L. Yang, E. L. Fleishaker, M. R. Ward, S. U. Monrad, P. C. Kottangada, C. Q. Pace, J. A. Clark, J. G. Woodward, et al. Defective Generation of a Humoral Immune Response Is Associated with a Reduced Incidence and Severity of Collagen-Induced Arthritis in Microsomal Prostaglandin E Synthase-1 Null Mice J. Immunol., June 15, 2008; 180(12): 8361 - 8368. [Abstract] [Full Text] [PDF]