title: SOCS-3 Regulates Alveolar Bone Loss in Experimental Periodontitis.
abstract: The host immune response plays a key role in bacteria-induced alveolar bone resorption. Endogenous control of the magnitude and duration of inflammatory signaling is considered an important determinant of the extent of periodontal pathology. Suppressor of cytokine signaling (SOCS) proteins are inhibitors of cytokine signaling pathways and may play a role in restraining periodontal inflammation. We hypothesized that SOCS-3 regulates alveolar bone loss in experimental periodontitis. Periodontal bone loss was induced in 16-wk-old myeloid-specific SOCS-3-knockout and wild-type (WT) C57Bl6-B.129 mice by oral inoculation 9 times with 10(9) colony-forming units of Porphyromonas gingivalis A7436 through an oral gavage model for periodontitis. Sham controls for both types of mice received vehicle without bacteria. The mice were euthanized 6 wk after the last oral inoculation. Increased bone loss was demonstrated in P. gingivalis-infected SOCS-3-knockout mice as compared with P. gingivalis-infected WT mice by direct morphologic measurements, micro-computed tomography analyses, and quantitative histology. Loss of SOCS-3 function resulted in an increased number of alveolar bone osteoclasts and increased RANKL expression after P. gingivalis infection. SOCS-3 deficiency in myeloid cells also promotes a higher P. gingivalis lipopolysaccharide-induced inflammatory response with higher secretion of IL-1β, IL-6, and KC (IL-8) by peritoneal macrophages as compared with WT controls. Our data implicate SOCS-3 as a critical negative regulator of alveolar bone loss in periodontitis.
authors.affiliation: Department of Applied Oral Sciences, Center for Periodontology, Forsyth Institute, Cambridge, MA, USA Department of Periodontology, Tufts University School of Dental Medicine, Boston, MA, USA Department of Preventive Dentistry, Periodontology and Implant Biology, Dental School, Aristotle University of Thessaloniki, Thessaloniki, Greece.
authors.forename: E
authors.initials: E
authors.lastname: Papathanasiou
authors.affiliation: Department of Applied Oral Sciences, Center for Periodontology, Forsyth Institute, Cambridge, MA, USA.
authors.forename: A
authors.initials: A
authors.lastname: Kantarci
authors.affiliation: Department of Preventive Dentistry, Periodontology and Implant Biology, Dental School, Aristotle University of Thessaloniki, Thessaloniki, Greece.
authors.forename: A
authors.initials: A
authors.lastname: Konstantinidis
authors.affiliation: Center for Experimental Therapeutics and Reperfusion Injury, Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: H
authors.initials: H
authors.lastname: Gao
authors.affiliation: Department of Applied Oral Sciences, Center for Periodontology, Forsyth Institute, Cambridge, MA, USA tvandyke@forsyth.org.
authors.forename: T E
authors.initials: TE
authors.lastname: Van Dyke
mesh_terms: D016301:Alveolar Bone Loss / Q000000981:diagnostic imaging / Q000473:pathology / Q000503:physiopathology*; D000818:Animals; D004195:Disease Models, Animal; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010010:Osteoclasts / Q000502:physiology; D010518:Periodontitis / Q000473:pathology / Q000503:physiopathology*; D016966:Porphyromonas gingivalis; D000071223:Suppressor of Cytokine Signaling 3 Protein / Q000502:physiology*; D050826:Suppressor of Cytokine Signaling Proteins / Q000502:physiology*; D055114:X-Ray Microtomography
chemical_list: C491411:Socs3 protein, mouse; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins
keywords: Porphyromonas gingivalis; animal model; cytokines; inflammation; macrophages; osteoclasts