title: Porphyromonas gingivalis regulates the RANKL-OPG system in bone marrow stromal cells.
abstract: Porphyromonas gingivalis is a Gram-negative anaerobe implicated in chronic periodontitis, a bacterial-induced inflammatory condition that causes destruction of the periodontal connective tissues and underlying alveolar bone. The receptor activator of nuclear factor-kappaB ligand (RANKL) is a cytokine that directly stimulates osteoclastogenesis and bone resorption, whereas its decoy receptor osteoprotegerin (OPG) blocks this action. This study aimed to investigate the effects of P. gingivalis culture supernatants on RANKL and OPG expression in W20-17 bone marrow stromal cells, and evaluate the involvement of its virulence factors, particularly gingipains and lipopolysaccharide. P. gingivalis up-regulated RANKL and down-regulated OPG mRNA expression and protein production. These effects were blocked by indomethacin, suggesting mediation by prostaglandins. Furthermore, P gingivalis induced the production of prostaglandin E(2). Heat-inactivation, or chemical inhibition of P. gingivalis gingipains did not affect RANKL and OPG regulation. However, lipopolysaccharide depletion by polymyxin B abolished RANKL induction, and partly rescued the suppression of OPG. In conclusion, P. gingivalis regulates the RANKL-OPG system via prostaglandin E(2) in bone marrow stromal cells, in a manner that favours osteoclastogenesis. A non-proteolytic and non-proteinaceous P. gingivalis component is involved in these events, most probably its lipopolysaccharide. This activity may contribute to the bone loss characteristic of periodontitis.
authors.affiliation: Institute of Dentistry, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, E1 2AD, UK.
authors.forename: Durga
authors.initials: D
authors.lastname: Reddi
authors.forename: Nagihan
authors.initials: N
authors.lastname: Bostanci
authors.forename: Ahmed
authors.initials: A
authors.lastname: Hashim
authors.forename: Joseph
authors.initials: J
authors.lastname: Aduse-Opoku
authors.forename: Michael A
authors.initials: MA
authors.lastname: Curtis
authors.forename: Francis J
authors.initials: FJ
authors.lastname: Hughes
authors.forename: Georgios N
authors.initials: GN
authors.lastname: Belibasakis
mesh_terms: D000818:Animals; D001853:Bone Marrow / Q000276:immunology* / Q000382:microbiology; D015536:Down-Regulation; D020869:Gene Expression Profiling; D051379:Mice; D053244:Osteoprotegerin / Q000096:biosynthesis* / Q000235:genetics; D016966:Porphyromonas gingivalis / Q000276:immunology*; D011453:Prostaglandins / Q000378:metabolism; D053245:RANK Ligand / Q000096:biosynthesis* / Q000235:genetics; D017154:Stromal Cells / Q000276:immunology* / Q000382:microbiology; D015854:Up-Regulation
chemical_list: D053244:Osteoprotegerin; D011453:Prostaglandins; D053245:RANK Ligand; C505689:Tnfsf11 protein, mouse