Anti-inflammatory and anti-osteoclastogenic effects of zinc finger protein A20 overexpression in human periodontal ligament cells.
J Periodontal Res
; 51(4): 529-39, 2016 Aug.
Article
en En
| MEDLINE
| ID: mdl-26548452
ABSTRACT
BACKGROUND AND OBJECTIVE:
Although overexpression of the nuclear factor κB inhibitory and ubiquitin-editing enzyme A20 is thought to be involved in the pathogenesis of inflammatory diseases, its function in periodontal disease remains unknown. The aims of the present study were to evaluate A20 expression in patients with periodontitis and to study the effects of A20 overexpression, using a recombinant adenovirus encoding A20 (Ad-A20), on the inflammatory response and on osteoclastic differentiation in lipopolysaccharide (LPS)- and nicotine-stimulated human periodontal ligament cells (hPDLCs). MATERIAL ANDMETHODS:
The concentration of prostaglandin E2 was measured by radioimmunoassay. Reverse transcription-polymerase chain reactions and western blot analyses were used to measure mRNA and protein levels, respectively. Osteoclastic differentiation was assessed in mouse bone marrow-derived macrophages using conditioned medium from LPS- and nicotine-treated hPDLCs.RESULTS:
A20 was upregulated in the gingival tissues and neutrophils from patients with periodontitis and in LPS- and nicotine-exposed hPDLCs. Pretreatment with A20 overexpression by Ad-A20 markedly attenuated LPS- and nicotine-induced production of prostaglandin E2 , as well as expression of cyclooxygenase-2 and proinflammatory cytokines. Moreover, A20 overexpression inhibited the number and size of tartrate-resistant acid phosphatase-stained osteoclasts, and downregulated osteoclast-specific gene expression. LPS- and nicotine-induced p38 phosphorylation and nuclear factor κB activation were blocked by Ad-A20. Ad-A20 inhibited the effects of nicotine and LPS on the activation of pan-protein kinase C, Akt, GSK-3ß and protein kinase Cα.CONCLUSIONS:
This study is the first to demonstrate that A20 overexpression has anti-inflammatory effects and blocks osteoclastic differentiation in a nicotine- and LPS-stimulated hPDLC model. Thus, A20 overexpression may be a potential therapeutic target in inflammatory bone loss diseases, such as periodontal disease.Palabras clave
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Base de datos:
MEDLINE
Asunto principal:
Osteoclastos
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Ligamento Periodontal
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Proteína 3 Inducida por el Factor de Necrosis Tumoral alfa
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Encía
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Antiinflamatorios
Tipo de estudio:
Prognostic_studies
Idioma:
En
Revista:
J Periodontal Res
Año:
2016
Tipo del documento:
Article