title: PPAR-gamma agonist rosiglitazone prevents inflammatory periodontal bone loss by inhibiting osteoclastogenesis.
abstract: Rosiglitazone (RGZ), an oral anti-hyperglycemic agent used for non-insulin-dependent diabetes mellitus, is a high-affinity synthetic agonist for peroxisome proliferator-activated receptor-gamma (PPAR-gamma). Both in vitro and in vivo experiments have also revealed that RGZ possesses anti-inflammatory properties. Therefore, in the present study, we investigated the anti-inflammatory effects of RGZ in a rat model of periodontal disease induced by ligature placed around the mandible first molars of each animal. Male Wister rats were divided into four groups: 1) animals without ligature placement receiving administration of empty vehicle (control); 2) animals with ligature receiving administration of empty vehicle; 3) animals with ligature receiving administration with oral RGZ (10 mg/kg/day); and 4) animals with ligature receiving administration of subcutaneous RGZ (10 mg/kg/day). Thirty days after induction of periodontal disease, the animals were sacrificed, and mandibles and gingival tissues were removed for further analysis. An in vitro assay was also employed to test the inhibitory effects of RGZ on osteoclastogenesis. Histomorphological and immunohistochemical analyses of periodontal tissue demonstrated that RGZ-treated animals presented decreased bone resorption, along with reduced RANKL expression, compared to those animals with ligature, but treated with empty vehicle. Corresponding to such results obtained from in vivo experiments, RGZ also suppressed in vitro osteoclast differentiation in the presence of RANKL in MOCP-5 osteoclast precursor cells, along with the down-regulation of the expression of RANKL-induced TRAP mRNA. These data indicated that RGZ may suppress the bone resorption by inhibiting RANKL-mediated osteoclastogenesis elicited during the course of experimental periodontitis in rats.
authors.affiliation: Laboratory of Biopathology and Molecular Biology, University of Uberaba, Minas Gerais, Brazil.
authors.forename: Márcio Y
authors.initials: MY
authors.lastname: Hassumi
authors.forename: Vilmar J
authors.initials: VJ
authors.lastname: Silva-Filho
authors.forename: Jozafá C
authors.initials: JC
authors.lastname: Campos-Júnior
authors.forename: Silvio M
authors.initials: SM
authors.lastname: Vieira
authors.forename: Fernando Q
authors.initials: FQ
authors.lastname: Cunha
authors.forename: Polyanna M
authors.initials: PM
authors.lastname: Alves
authors.forename: José B
authors.initials: JB
authors.lastname: Alves
authors.forename: Toshihisa
authors.initials: T
authors.lastname: Kawai
authors.forename: Reginaldo B
authors.initials: RB
authors.lastname: Gonçalves
authors.forename: Marcelo H
authors.initials: MH
authors.lastname: Napimoga
mesh_terms: D000135:Acid Phosphatase / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D000284:Administration, Oral; D016301:Alveolar Bone Loss / Q000517:prevention & control; D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D007004:Hypoglycemic Agents / Q000008:administration & dosage* / Q000494:pharmacology; D007150:Immunohistochemistry; D007527:Isoenzymes / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D008297:Male; D010010:Osteoclasts / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D010012:Osteogenesis / Q000187:drug effects; D047495:PPAR gamma / Q000819:agonists; D010518:Periodontitis / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology / Q000503:physiopathology; D053245:RANK Ligand / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D000077154:Rosiglitazone; D000071681:Tartrate-Resistant Acid Phosphatase; D045162:Thiazolidinediones / Q000008:administration & dosage* / Q000494:pharmacology
chemical_list: D007004:Hypoglycemic Agents; D007527:Isoenzymes; D047495:PPAR gamma; D053245:RANK Ligand; D045162:Thiazolidinediones; D000077154:Rosiglitazone; D000135:Acid Phosphatase; D000071681:Tartrate-Resistant Acid Phosphatase