title: Simvastatin as a novel strategy to alleviate periapical lesions.
abstract: Hydroxymethylglutaryl-coenzyme A reductase inhibitors (statins) are widely used cholesterol-lowering agents that also possess anti-inflammatory activities. Cysteine-rich 61 (Cyr61) and CCL2 are potential osteolytic mediators in inflammatory bone diseases. The study assessed the effect of simvastatin on tumor necrosis factor alpha (TNF- alpha)-induced synthesis of Cyr61 and CCL2 in MG-63 human osteoblastic cells. The therapeutic effect of simvastatin on rat apical periodontitis was also examined. The synthesis of Cyr61 in MG-63 was assessed by Western analysis. Expression of CCL2 was examined by an enzyme-linked immunosorbent assay. The effect of simvastatin on induced rat periapical lesion was examined radiographically and immunohistochemically. Western blot showed that TNF-alpha stimulated Cyr61 synthesis in MG-63, whereas simvastatin attenuated this effect in a dose-dependent manner. Simvastatin also reduced the levels of TNF-alpha-induced CCL2, and exogenous Cyr61 restored the inhibitory effects. Radiography and histopathology revealed that the administration of simvastatin markedly diminished the severity of induced rat periapical lesions. The numbers of Cyr61-synthesizing osteoblasts and CD-68-positive macrophages were also decreased. Simvastatin suppresses the progression of apical periodontitis, possibly by diminishing Cyr61 expression in osteoblasts and, subsequently, macrophage chemotaxis into the lesions.
authors.affiliation: School of Dentistry, College of Medicine, National Taiwan University, Taipei, Taiwan.
authors.forename: Sze-Kwan
authors.initials: SK
authors.lastname: Lin
authors.forename: Sang-Heng
authors.initials: SH
authors.lastname: Kok
authors.forename: Yuan-Ling
authors.initials: YL
authors.lastname: Lee
authors.forename: Kuo-Liang
authors.initials: KL
authors.lastname: Hou
authors.forename: Yi-Ting
authors.initials: YT
authors.lastname: Lin
authors.forename: Mu-Hsiung
authors.initials: MH
authors.lastname: Chen
authors.forename: Chih-Chiang
authors.initials: CC
authors.lastname: Wang
authors.forename: Chi-Yuan
authors.initials: CY
authors.lastname: Hong
mesh_terms: D016301:Alveolar Bone Loss / Q000000981:diagnostic imaging / Q000188:drug therapy; D000818:Animals; D015703:Antigens, CD / Q000187:drug effects; D015214:Antigens, Differentiation, Myelomonocytic / Q000187:drug effects; D015153:Blotting, Western; D002452:Cell Count; D002460:Cell Line; D018932:Chemokine CCL2 / Q000037:antagonists & inhibitors / Q000187:drug effects; D002633:Chemotaxis / Q000187:drug effects; D055515:Cysteine-Rich Protein 61 / Q000037:antagonists & inhibitors / Q000187:drug effects; D004195:Disease Models, Animal; D018450:Disease Progression; D004305:Dose-Response Relationship, Drug; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D007150:Immunohistochemistry; D008264:Macrophages / Q000187:drug effects; D010006:Osteoblasts / Q000187:drug effects; D010485:Periapical Periodontitis / Q000000981:diagnostic imaging / Q000188:drug therapy*; D019252:Radiography, Dental, Digital; D051381:Rats; D017207:Rats, Sprague-Dawley; D019821:Simvastatin / Q000494:pharmacology / Q000627:therapeutic use*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D000097382:CD68 Molecule
chemical_list: D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D018932:Chemokine CCL2; D055515:Cysteine-Rich Protein 61; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D019821:Simvastatin; D014409:Tumor Necrosis Factor-alpha; C111835:CCL2 protein, human; C501848:CCN1 protein, human; C067980:CD68 antigen, human; D000097382:CD68 Molecule