title: ST2 deletion increases inflammatory bone destruction in experimentally induced periapical lesions in mice.
abstract: BACKGROUND
  ST2 is a member of the interleukin (IL)-1 receptor family, and IL-33 is its natural ligand. ST2 signaling promotes Th2 immune response in allergy, autoimmunity, and chronic inflammatory disorders, but its role in the pathogenesis of periapical lesions is unknown. The purpose of this study was to investigate whether ST2 gene deletion affects the development of experimentally induced periapical lesions in mice.
  
  
  METHODS
  Pulps of mandibular molars from wild-type (WT) and ST2 knockout (ST2(-)/(-)) BALB/c mice were exposed and left open to the oral environment. After death, hemi-mandibles were isolated and prepared for histologic, immunohistochemical, and flow cytometric analysis.
  
  
  RESULTS
  The expression of IL-33 and its receptor ST2 was higher in periapical lesions in WT mice compared with normal root apices (both P < .05). The increased periapical bone loss observed in ST2(-)/(-) mice was associated with enhanced influx of neutrophils, CD3+ CXCR3+ Th1 cells, and CD3+ CCR6+ Th17 cells and increased number of tartrate-resistant acid phosphatase+ osteoclasts (all P < .05). Furthermore, periapical lesions in ST2(-)/(-) mice contained increased percentages of T cells expressing interferon-γ, IL-17, tumor necrosis factor-α, and IL-6 (all P < .05). In comparison with WT mice, CD3+ receptor activator of nuclear factor kappa B ligand+ T cells were increased, whereas CD3+ osteoprotegerin+ T cells were decreased in the lesions of ST2(-)/(-) mice (both P < .05).
  
  
  CONCLUSIONS
  ST2 deletion increases inflammatory bone loss in experimental periapical lesions in mice, which is associated with enhanced Th1/Th17 cell mediated periapical immune responses and increased osteoclastogenesis.
authors.affiliation: Center for Molecular Medicine, Kragujevac, Serbia.
authors.forename: Milena
authors.initials: M
authors.lastname: Velickovic
authors.affiliation: Center for Molecular Medicine, Kragujevac, Serbia.
authors.forename: Nada
authors.initials: N
authors.lastname: Pejnovic
authors.affiliation: Center for Molecular Medicine, Kragujevac, Serbia.
authors.forename: Slobodanka
authors.initials: S
authors.lastname: Mitrovic
authors.affiliation: Center for Molecular Medicine, Kragujevac, Serbia.
authors.forename: Gordana
authors.initials: G
authors.lastname: Radosavljevic
authors.affiliation: Center for Molecular Medicine, Kragujevac, Serbia.
authors.forename: Ivan
authors.initials: I
authors.lastname: Jovanovic
authors.affiliation: Department of Preventive and Pediatric Dentistry, Faculty of Medical Sciences, University of Kragujevac, Kragujevac, Serbia.
authors.forename: Tatjana
authors.initials: T
authors.lastname: Kanjevac
authors.affiliation: Center for Molecular Medicine, Kragujevac, Serbia.
authors.forename: Nemanja
authors.initials: N
authors.lastname: Jovicic
authors.affiliation: Department of Endodontics, Faculty of Medical Sciences, University of Kragujevac, Kragujevac, Serbia. Electronic address: miodrag.lukic@medf.kg.ac.rs.
authors.forename: Aleksandra
authors.initials: A
authors.lastname: Lukic
mesh_terms: D000818:Animals; D001842:Bone and Bones / Q000473:pathology*; D002452:Cell Count; D003782:Dental Pulp / Q000473:pathology; D005434:Flow Cytometry; D017353:Gene Deletion; D007249:Inflammation / Q000473:pathology*; D000072179:Interleukin-1 Receptor-Like 1 Protein / Q000172:deficiency* / Q000378:metabolism; D000067596:Interleukin-33 / Q000378:metabolism; D008198:Lymph Nodes / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D010010:Osteoclasts / Q000378:metabolism / Q000473:pathology; D010486:Periapical Tissue / Q000473:pathology*; D000071681:Tartrate-Resistant Acid Phosphatase / Q000378:metabolism; D018417:Th1 Cells / Q000276:immunology; D058504:Th17 Cells / Q000276:immunology
chemical_list: C486189:Il1rl1 protein, mouse; D000072179:Interleukin-1 Receptor-Like 1 Protein; D000067596:Interleukin-33; D000071681:Tartrate-Resistant Acid Phosphatase
keywords: Bone loss; RANKL; ST2; Th1/Th17 cells; inflammation; osteoclasts; periapical lesions