title: Receptor activator NF kappaB ligand (RANKL) and osteoprotegerin (OPG) protein expression in periodontitis.
abstract: OBJECTIVE
  This study investigated the expression of key mediators that regulate differentiation of osteoclasts, receptor activator of nuclear factor kappaB ligand (RANKL), and its natural inhibitor, osteoprotegerin (OPG), in periodontitis. We aimed to compare the levels of the RANKL and OPG in the granulomatous tissue adjacent to areas of alveolar bone loss from patients with periodontitis to that present in tissue from patients without periodontitis. In addition, we aimed to determine the types of cells expressing these factors in these tissues and to demonstrate the expression of the osteoclastic markers, RANK and tartrate-resistant acid phosphatase (TRAP), in periodontitis.
  
  
  METHODS
  Frozen biopsy specimens were analysed using specific monoclonal antibodies and were evaluated by semiquantitative analysis and digital image analysis to compare levels of RANKL and OPG protein expression. Double labelling of frozen sections with antibodies to different cell lineage specific markers was used to determine the types of cells expressing these proteins. In situ hybridization was used to detect cells expressing RANK mRNA.
  
  
  RESULTS
  Semiquantitative image analysis demonstrated that significantly higher levels of RANKL protein (P < 0.05) were expressed in the periodontitis tissue. Conversely, OPG protein was significantly lower (P < 0.05) in the periodontitis tissues. RANKL protein was associated with lymphocytes and macrophages. OPG protein was associated with endothelial cells in both tissues. Many leukocytes expressing RANK mRNA and TRAP were observed in periodontitis tissues.
  
  
  CONCLUSIONS
  The change in the levels of these key regulators of osteoclast differentiation may play a major role in the bone loss seen in periodontitis.
authors.affiliation: Department of Pathology, University of Adelaide, Adelaide, Australia.
authors.forename: Tania
authors.initials: T
authors.lastname: Crotti
authors.forename: Malcolm D
authors.initials: MD
authors.lastname: Smith
authors.forename: Robert
authors.initials: R
authors.lastname: Hirsch
authors.forename: Steven
authors.initials: S
authors.lastname: Soukoulis
authors.forename: Helen
authors.initials: H
authors.lastname: Weedon
authors.forename: Maria
authors.initials: M
authors.lastname: Capone
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Ahern
authors.forename: David
authors.initials: D
authors.lastname: Haynes
mesh_terms: D000135:Acid Phosphatase / Q000032:analysis; D000293:Adolescent; D000328:Adult; D000368:Aged; D016301:Alveolar Bone Loss / Q000378:metabolism; D015415:Biomarkers / Q000032:analysis; D002352:Carrier Proteins / Q000032:analysis*; D002454:Cell Differentiation; D004730:Endothelium, Vascular / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation; D006023:Glycoproteins / Q000032:analysis*; D006801:Humans; D007527:Isoenzymes / Q000032:analysis; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D008024:Ligands; D008297:Male; D008562:Membrane Glycoproteins / Q000032:analysis*; D008875:Middle Aged; D016328:NF-kappa B / Q000032:analysis*; D010010:Osteoclasts / Q000378:metabolism; D053244:Osteoprotegerin; D010518:Periodontitis / Q000378:metabolism*; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; D018160:Receptors, Cytoplasmic and Nuclear / Q000032:analysis*; D018124:Receptors, Tumor Necrosis Factor / Q000032:analysis*; D000071681:Tartrate-Resistant Acid Phosphatase
chemical_list: D015415:Biomarkers; D002352:Carrier Proteins; D006023:Glycoproteins; D007527:Isoenzymes; D008024:Ligands; D008562:Membrane Glycoproteins; D016328:NF-kappa B; D053244:Osteoprotegerin; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; D018160:Receptors, Cytoplasmic and Nuclear; D018124:Receptors, Tumor Necrosis Factor; C505686:TNFRSF11A protein, human; C506030:TNFRSF11B protein, human; C505688:TNFSF11 protein, human; D000135:Acid Phosphatase; D000071681:Tartrate-Resistant Acid Phosphatase