The role of cyclooxygenase-2 (COX-2) in inflammatory bone resorption.
Prostaglandin E2 (PGE(2)) is an important inflammatory mediator that plays an essential role in the development and progression of periradicular diseases. Cyclooxygenase-2 (COX-2) is the inducible enzyme responsible for increased PGE(2) levels during inflammation and other pathologic processes. The purpose of this study was to determine the role of COX-2-mediated PGE(2) synthesis in osteoclast formation in response to endodontic pathogens and materials. Primary osteoblast cultures and osteoclast cultures were prepared from COX-2 knockout (K/O) and wild-type (WT) littermates. These cultured cells were exposed to lipopolysaccharide (LPS) or root canal obturation materials including gutta-percha (GP), Resilon (RS), mineral trioxide aggregates (MTAs), and AH Plus (AH+). Osteoclast formation was evaluated using tartrate-resistant acid phosphatase (TRAP) staining. The expression of receptor activator of NF-kappaB ligand (RANKL) and osteoprotegerin (OPG) was determined by real-time polymerase chain reaction (PCR) analysis. It was found that in both WT and K/O cultures, treatment with LPS led to a marked increase in osteoclast formation. The number of osteoclasts formed was significantly lower in K/O cultures compared to WT cultures. Exposure to endodontic materials did not lead to any significant osteoclast formation. LPS and endodontic materials caused a decrease in both RANKL and OPG expression in WT cells. In K/O cells, the baseline levels of RANKL and OPG expression were dramatically decreased compared to the WT cells. In conclusion, COX-2-mediated PGE(2) expression is required for LPS-induced inflammatory bone resorption and maintaining the baseline level of RANKL and OPG expression. LPS-induced osteoclast formation may be independent of the RANKL pathway.
Coon
David
D
Department of Endodontics, Biomedical Sciences, Baylor College of Dentistry, The Texas A&M University System Health Science Center, Dallas, TX, USA.
Gulati
Ajay
A
Cowan
Cameron
C
He
Jianing
J
D000135:Acid Phosphatase / Q000032:analysis; D017607:Aluminum Compounds / Q000494:pharmacology; D000818:Animals; D015415:Biomarkers / Q000032:analysis; D001862:Bone Resorption / Q000201:enzymology*; D017610:Calcium Compounds / Q000494:pharmacology; D002478:Cells, Cultured; D051546:Cyclooxygenase 2 / Q000502:physiology*; D015232:Dinoprostone / Q000096:biosynthesis; D004338:Drug Combinations; D004853:Epoxy Resins / Q000494:pharmacology; D005260:Female; D006171:Gutta-Percha / Q000494:pharmacology; D018836:Inflammation Mediators / Q000378:metabolism; D007527:Isoenzymes / Q000032:analysis; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D010000:Osteitis / Q000201:enzymology*; D010006:Osteoblasts / Q000201:enzymology; D010010:Osteoclasts / Q000201:enzymology; D053244:Osteoprotegerin / Q000032:analysis; D010087:Oxides / Q000494:pharmacology; D053245:RANK Ligand / Q000032:analysis; D012387:Root Canal Filling Materials / Q000494:pharmacology; D017640:Silicates / Q000494:pharmacology; D000071681:Tartrate-Resistant Acid Phosphatase
D017607:Aluminum Compounds; D015415:Biomarkers; D017610:Calcium Compounds; D004338:Drug Combinations; D004853:Epoxy Resins; D018836:Inflammation Mediators; D007527:Isoenzymes; D008070:Lipopolysaccharides; D053244:Osteoprotegerin; D010087:Oxides; D053245:RANK Ligand; D012387:Root Canal Filling Materials; D017640:Silicates; C506031:Tnfrsf11b protein, mouse; C505689:Tnfsf11 protein, mouse; C534916:epoxy resin-based root canal sealer; C086631:mineral trioxide aggregate; C486892:resilon sealer; D006171:Gutta-Percha; D051546:Cyclooxygenase 2; D000135:Acid Phosphatase; C000605511:Acp5 protein, mouse; D000071681:Tartrate-Resistant Acid Phosphatase; D015232:Dinoprostone