title: Osteoprotective Effects of IL-33/ST2 Link to Osteoclast Apoptosis.
abstract: The relevance of IL-33 and its receptor ST2 for bone remodeling is not well-defined. Our aim was to assess the role and underlying mechanisms of IL-33/ST2 in mechanically induced bone remodeling. BALB/c (wild type) and ST2 deficient (St2(-/-)) mice were subjected to mechanical loading in alveolar bone. Microtomography, histology, and real-time quantitative PCR were performed to analyze bone parameters, apoptosis and bone cell counts, and expression of bone remodeling markers, respectively. MC3T3-E1 osteoblastic cells and bone marrow cells were used to verify if mechanical force triggered IL-33 and ST2 expression as well as the effects of IL-33 on osteoclast differentiation and activity. Mechanical loading increased the expression of IL-33 and ST2 in alveolar bone in vivo and in osteoblastic cells in vitro. St2(-/-) mice had increased mechanical loading-induced bone resorption, number of osteoclasts, and expression of proresorptive markers. In contrast, St2(-/-) mice exhibited reduced numbers of osteoblasts and apoptotic cells in periodontium and diminished expression of osteoblast signaling molecules. In vitro, IL-33 treatment inhibited osteoclast differentiation and activity even in the presence of receptor activator of NF-κB ligand. IL-33 also increased the expression of pro-apoptotic molecules, including Bcl-2-associated X protein (BAX), cell-surface Fas receptor (FAS), FASL, FAS-associated death domain, tumor necrosis factor-related apoptosis-inducing ligand, and BH3 interacting-domain death (BID). Overall, these findings suggest that IL-33/ST2 have anti-osteoclastogenic effects and reduce osteoclast formation and activity by inducing their apoptosis.
authors.affiliation: Department of Biochemistry and Immunology, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
authors.forename: Izabella L A
authors.initials: IL
authors.lastname: Lima
authors.affiliation: Department of Biochemistry and Immunology, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
authors.forename: Soraia
authors.initials: S
authors.lastname: Macari
authors.affiliation: Department of Oral Pathology, Faculty of Dentistry, Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
authors.forename: Mila F M
authors.initials: MF
authors.lastname: Madeira
authors.affiliation: Department of Oral Pathology, Faculty of Dentistry, Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
authors.forename: Letícia F D
authors.initials: LF
authors.lastname: Rodrigues
authors.affiliation: Department of Biological Sciences, Bauru School of Dentistry, University of São Paulo, Bauru, São Paulo, Brazil.
authors.forename: Priscila M
authors.initials: PM
authors.lastname: Colavite
authors.affiliation: Department of Biological Sciences, Bauru School of Dentistry, University of São Paulo, Bauru, São Paulo, Brazil.
authors.forename: Gustavo P
authors.initials: GP
authors.lastname: Garlet
authors.affiliation: Department of General Biology, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
authors.forename: Frederico M
authors.initials: FM
authors.lastname: Soriani
authors.affiliation: Department of Biochemistry and Immunology, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
authors.forename: Mauro M
authors.initials: MM
authors.lastname: Teixeira
authors.affiliation: School of Medicine of Ribeirao Preto, and the Department of Physics and Chemistry, Faculty of Pharmaceutical Sciences of Ribeirão Preto, São Paulo University, São Paulo, Brazil.
authors.forename: Sandra Y
authors.initials: SY
authors.lastname: Fukada
authors.affiliation: Department of Oral Pathology, Faculty of Dentistry, Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, Brazil. Electronic address: tarcilia@ufmg.br.
authors.forename: Tarcília A
authors.initials: TA
authors.lastname: Silva
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D015415:Biomarkers / Q000378:metabolism; D015519:Bone Density / Q000502:physiology; D016723:Bone Remodeling / Q000502:physiology*; D001862:Bone Resorption / Q000503:physiopathology; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D000072179:Interleukin-1 Receptor-Like 1 Protein; D000067596:Interleukin-33 / Q000096:biosynthesis / Q000494:pharmacology / Q000502:physiology*; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D010010:Osteoclasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D010519:Periodontium / Q000378:metabolism / Q000473:pathology; D018123:Receptors, Interleukin / Q000096:biosynthesis / Q000172:deficiency / Q000502:physiology*; D013314:Stress, Mechanical; D016474:Weight-Bearing
chemical_list: D015415:Biomarkers; C486189:Il1rl1 protein, mouse; C506535:Il33 protein, mouse; D000072179:Interleukin-1 Receptor-Like 1 Protein; D000067596:Interleukin-33; D018123:Receptors, Interleukin