title: Adenosine receptor stimulation by polynucleotides (PDRN) reduces inflammation in experimental periodontitis.
abstract: OBJECTIVE
  Adenosine receptors modulate inflammation in periodontal tissues. No data are available regarding the effects of adenosine A(2A)  receptor stimulation in experimental periodontitis (EPD). The aim of this study was to investigate the effects of polynucleotides (also known as polydeoxyribonucleotide, PDRN), a ligand of A(2A)  receptor, in EPD in rats.
  
  
  METHODS
  EPD was induced ligating the cervix of the lower left first molar. Sham-EPD had no ligature. After 7 days, EPD animals were randomized to a daily treatment with vehicle gel or 0.75% PDRN gel or PDRN gel with a specific A(2A)  antagonist (DMPX). Treatments lasted 7 days. Animals were then euthanized and the periodontium and surrounding gingival tissue were excised for histological evaluation and bio-molecular analysis of inflammatory (p-JNK, p-ERK, TNF-α, IL-6, HMGB-1) and apoptotic proteins (BAX and Bcl-2).
  
  
  RESULTS
  Vehicle-treated EPD rats showed severe inflammatory infiltrate in both gingival and periodontal ligament, as well as an enhanced expression of p-JNK, p-ERK, TNF-α, IL-6, HMGB-1 and BAX and a reduction in Bcl-2. PDRN gel restored the histological features, blunted inflammatory and apoptotic proteins expression and preserved Bcl-2 expression. DMPX abrogated PDRN positive effects.
  
  
  CONCLUSIONS
  Our data suggest that adenosine receptor stimulation by PDRN might represent a new therapeutic strategy for periodontitis.
authors.affiliation: Department of Experimental and Clinical Medicine and Pharmacology, Section of Pharmacology, University of Messina, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Bitto
authors.forename: Giacomo
authors.initials: G
authors.lastname: Oteri
authors.forename: Michele
authors.initials: M
authors.lastname: Pisano
authors.forename: Francesca
authors.initials: F
authors.lastname: Polito
authors.forename: Natasha
authors.initials: N
authors.lastname: Irrera
authors.forename: Letteria
authors.initials: L
authors.lastname: Minutoli
authors.forename: Francesco
authors.initials: F
authors.lastname: Squadrito
authors.forename: Domenica
authors.initials: D
authors.lastname: Altavilla
mesh_terms: D058917:Adenosine A2 Receptor Antagonists / Q000494:pharmacology; D016301:Alveolar Bone Loss / Q000378:metabolism; D000818:Animals; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D024243:HMGB1 Protein / Q000378:metabolism; D018836:Inflammation Mediators / Q000494:pharmacology*; D015850:Interleukin-6 / Q000378:metabolism; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D008297:Male; D010518:Periodontitis / Q000378:metabolism*; D011089:Polydeoxyribonucleotides / Q000494:pharmacology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D018047:Receptors, Purinergic P1 / Q000187:drug effects*; D013805:Theobromine / Q000031:analogs & derivatives* / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: D058917:Adenosine A2 Receptor Antagonists; D024243:HMGB1 Protein; D018836:Inflammation Mediators; D015850:Interleukin-6; D011089:Polydeoxyribonucleotides; D019253:Proto-Oncogene Proteins c-bcl-2; D018047:Receptors, Purinergic P1; D014409:Tumor Necrosis Factor-alpha; D051028:bcl-2-Associated X Protein; C057837:3,7-dimethyl-1-propargylxanthine; D048049:Extracellular Signal-Regulated MAP Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D013805:Theobromine