Toll-like receptor 2 heterodimers, TLR2/6 and TLR2/1 induce prostaglandin E production by osteoblasts, osteoclast formation and inflammatory periodontitis.
TLR2 forms heterodimers with TLR1 and TLR6, and regulates host defense mechanisms against pathogens. We examined the role of TLR2 heterodimer signaling in osteoclast formation and inflammatory periodontitis. In co-cultures of mouse bone marrow cells and osteoblasts, a TLR2/6 ligand (diacylated lipopeptide designed from Gram-positive bacteria) markedly induced osteoclast formation. A TLR2/1 ligand (triacylated lipopeptide designed from Gram-negative bacteria) also induced osteoclast formation. The osteoclast formation induced by TLR2/6 and TLR2/1 ligands was completely suppressed by indomethacin. Osteoblasts expressed TLR1, 2, 4, and 6 mRNAs, and both TLR2/6 and TLR2/1 ligands induced the expression of COX-2, mPGES-1, and RANKL mRNA, as well as PGE production in osteoblasts. Both TLR2/6 and TLR2/1 ligands induced the resorption of mandibular alveolar bone in organ cultures, and elicited inflammatory periodontitis in vivo. Therefore, TLR2 heterodimer signaling may play a key role in PGE-mediated inflammatory bone loss in periodontal disease.
Department of Biotechnology and Life Science, Tokyo University of Agriculture and Technology, 2-24-16 Nakamachi, Koganei, Tokyo 184-8588, Japan.
Chiho
C
Matsumoto
Toshio
T
Oda
Satoshi
S
Yokoyama
Tsukasa
T
Tominari
Michiko
M
Hirata
Chisato
C
Miyaura
Masaki
M
Inada
D000818:Animals; D001854:Bone Marrow Cells / Q000378:metabolism; D002478:Cells, Cultured; D018920:Coculture Techniques; D051546:Cyclooxygenase 2 / Q000096:biosynthesis; D004195:Disease Models, Animal; D019746:Intramolecular Oxidoreductases / Q000096:biosynthesis; D008024:Ligands; D051379:Mice; D008815:Mice, Inbred Strains; D010006:Osteoblasts / Q000378:metabolism*; D010518:Periodontitis / Q000378:metabolism* / Q000473:pathology; D000071876:Prostaglandin-E Synthases; D011458:Prostaglandins E / Q000096:biosynthesis*; D055503:Protein Multimerization; D053245:RANK Ligand / Q000096:biosynthesis; D012333:RNA, Messenger / Q000096:biosynthesis; D015398:Signal Transduction; D051195:Toll-Like Receptor 2 / Q000235:genetics / Q000378:metabolism*; D051216:Toll-Like Receptor 6 / Q000235:genetics / Q000378:metabolism*; D051193:Toll-Like Receptors / Q000235:genetics / Q000378:metabolism*
D008024:Ligands; D011458:Prostaglandins E; D053245:RANK Ligand; D012333:RNA, Messenger; C482903:Tlr11 protein, mouse; C493486:Tlr2 protein, mouse; C495369:Tlr6 protein, mouse; C505689:Tnfsf11 protein, mouse; D051195:Toll-Like Receptor 2; D051216:Toll-Like Receptor 6; D051193:Toll-Like Receptors; C077623:Ptgs2 protein, mouse; D051546:Cyclooxygenase 2; D019746:Intramolecular Oxidoreductases; D000071876:Prostaglandin-E Synthases; C000605865:Ptges protein, mouse