title: Regulation of RANKL and OPG gene expression in human gingival fibroblasts and periodontal ligament cells by Porphyromonas gingivalis: a putative role of the Arg-gingipains.
abstract: Porphyromonas gingivalis is highly implicated in the pathogenesis of periodontitis, which is characterized by the destruction of periodontal connective tissues and the supporting alveolar bone. Receptor Activator of NF-kappaB Ligand (RANKL) stimulates bone resorption, whereas osteoprotegerin (OPG) blocks its action, and this bi-molecular system is implicated in periodontitis. The aim of this work was (a) to investigate the regulation of RANKL and OPG gene expression in human periodontal ligament (PDL) cells and gingival fibroblasts (GF), in response to P. gingivalis culture supernatants, by quantitative real-time PCR and (b) to attempt to identify putative virulence factors involved in this process. The results indicated that P. gingivalis induced RANKL and reduced OPG mRNA expression by the studied cells, resulting in an increased RANKL/OPG expression ratio. Heat-inactivation of P. gingivalis resulted in significant reduction of RANKL mRNA expression. A Lys-gingipain mutant strain did not affect, whereas an Arg-gingipain mutant strain further enhanced RANKL mRNA expression, compared to their parental wild-type strain. In conclusion, P. gingivalis up-regulates the RANKL/OPG expression ratio in GF and PDL cells, denoting an enhanced osteoclastogenic potential by the cells. The component mainly responsible for RANKL induction appears to be proteinaceous, and it may be regulated by the Arg-gingipains.
authors: Centre for Adult Oral Health, Bart's and the London School of Medicine and Dentistry, Queen Mary's University of London, London E1 2AT, UK. g.belibasakis@qmul.ac.uk
authors: Georgios N
authors: GN
authors: Belibasakis
authors: Nagihan
authors: N
authors: Bostanci
authors: Ahmed
authors: A
authors: Hashim
authors: Anders
authors: A
authors: Johansson
authors: Joseph
authors: J
authors: Aduse-Opoku
authors: Michael A
authors: MA
authors: Curtis
authors: Francis J
authors: FJ
authors: Hughes
mesh_terms: D018829:Adhesins, Bacterial / Q000502:physiology*; D016866:Bacteroidaceae Infections / Q000382:microbiology*; D002460:Cell Line; D003546:Cysteine Endopeptidases / Q000502:physiology*; D005347:Fibroblasts / Q000382:microbiology; D017353:Gene Deletion; D005786:Gene Expression Regulation; D005798:Genes, Bacterial; D000080867:Gingipain Cysteine Endopeptidases; D005881:Gingiva / Q000166:cytology / Q000382:microbiology*; D006801:Humans; D053244:Osteoprotegerin / Q000235:genetics*; D010513:Periodontal Ligament / Q000382:microbiology*; D016966:Porphyromonas gingivalis / Q000472:pathogenicity*; D053245:RANK Ligand / Q000235:genetics*; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D037521:Virulence Factors / Q000502:physiology
chemical_list: D018829:Adhesins, Bacterial; D000080867:Gingipain Cysteine Endopeptidases; D053244:Osteoprotegerin; D053245:RANK Ligand; D012333:RNA, Messenger; C505688:TNFSF11 protein, human; D037521:Virulence Factors; D003546:Cysteine Endopeptidases