title: Porphyromonas gingivalis induces RANKL in bone marrow stromal cells: involvement of the p38 MAPK.
abstract: Periodontitis is a bacterially-induced oral inflammatory disease that is characterised by tissue degradation and bone loss. Porphyromonas gingivalis is a gram negative bacterial species highly associated with the pathogenesis of chronic periodontitis. Receptor activator of nuclear factor-kB ligand (RANKL) induces bone resorption whilst osteoprotegerin (OPG) is a decoy receptor that blocks this process. Cyclooxygenase-2 (COX-2) is an enzyme responsible for the production of prostaglandin (PGE)(2,) which is a major inflammatory mediator of bone resorption. Mitogen-activated protein kinases (MAPK) are intracellular signalling molecules involved in various cell processes, including inflammation. This study aimed to investigate the effect of P. gingivalis on MAPKs and their involvement in the regulation of RANKL, OPG and COX-2 expression in bone marrow stromal cells. P. gingivalis challenge resulted in the phosphorylation of primarily the p38 MAPK. RANKL and COX-2 mRNA expressions were up-regulated, whereas OPG was down-regulated by P. gingivalis. The p38 synthetic inhibitor SB203580 abolished the P. gingivalis-induced RANKL and COX-2 expression, but did not affect OPG. Collectively, these results suggest that the p38 MAPK pathway is involved in the induction of RANKL and COX-2 by P. gingivalis, providing further insights into the pathogenic mechanisms of periodontitis.
authors.affiliation: Institute of Dentistry, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, UK.
authors.forename: Durga
authors.initials: D
authors.lastname: Reddi
authors.forename: Stuart J
authors.initials: SJ
authors.lastname: Brown
authors.forename: Georgios N
authors.initials: GN
authors.lastname: Belibasakis
mesh_terms: D000818:Animals; D001853:Bone Marrow / Q000276:immunology / Q000382:microbiology* / Q000502:physiology*; D002460:Cell Line; D051546:Cyclooxygenase 2 / Q000096:biosynthesis; D020869:Gene Expression Profiling; D051379:Mice; D010766:Phosphorylation; D016966:Porphyromonas gingivalis / Q000276:immunology*; D053245:RANK Ligand / Q000096:biosynthesis*; D017154:Stromal Cells / Q000276:immunology / Q000382:microbiology* / Q000502:physiology*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
chemical_list: D053245:RANK Ligand; C505689:Tnfsf11 protein, mouse; C077623:Ptgs2 protein, mouse; D051546:Cyclooxygenase 2; D048051:p38 Mitogen-Activated Protein Kinases