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Silencing matrix metalloproteinase-13 (Mmp-13) reduces inflammatory bone resorption associated with LPS-induced periodontal disease in vivo.
Guimaraes-Stabili, Morgana R; de Medeiros, Marcell Costa; Rossi, Danuza; Camilli, Angelo Constantino; Zanelli, Cleslei Fernando; Valentini, Sandro Roberto; Spolidorio, Luis Carlos; Kirkwood, Keith Lough; Rossa, Carlos.
Afiliação
  • Guimaraes-Stabili MR; Department of Diagnosis and Surgery, School of Dentistry at Araraquara-State University of São Paulo UNESP, Rua Humaita, 1680, Centro, Araraquara, SP, 14801-903, Brazil. morgana.guimaraes@unesp.br.
  • de Medeiros MC; Department of Diagnosis and Surgery, School of Dentistry at Araraquara-State University of São Paulo UNESP, Rua Humaita, 1680, Centro, Araraquara, SP, 14801-903, Brazil.
  • Rossi D; Department of Biological Sciences, School of Pharmaceutical Sciences, UNESP, Araraquara, SP, Brazil.
  • Camilli AC; Department of Diagnosis and Surgery, School of Dentistry at Araraquara-State University of São Paulo UNESP, Rua Humaita, 1680, Centro, Araraquara, SP, 14801-903, Brazil.
  • Zanelli CF; Department of Biological Sciences, School of Pharmaceutical Sciences, UNESP, Araraquara, SP, Brazil.
  • Valentini SR; Department of Biological Sciences, School of Pharmaceutical Sciences, UNESP, Araraquara, SP, Brazil.
  • Spolidorio LC; Department of Physiology and Pathology, School of Dentistry at Araraquara, UNESP, Araraquara, SP, Brazil.
  • Kirkwood KL; Department of Oral Biology, University at Buffalo, State University of New York, Buffalo, NY, USA.
  • Rossa C; Department of Diagnosis and Surgery, School of Dentistry at Araraquara-State University of São Paulo UNESP, Rua Humaita, 1680, Centro, Araraquara, SP, 14801-903, Brazil.
Clin Oral Investig ; 25(5): 3161-3172, 2021 May.
Article em En | MEDLINE | ID: mdl-33140162
OBJECTIVES: The aim of this study was to evaluate the effect of specific inhibition of MMP-13 on inflammation and inflammatory bone resorption in a murine model of lipopolysaccharide (LPS)-induced periodontitis. MATERIALS AND METHODS: Periodontitis was induced in mice by micro-injections of LPS into the gingival tissues adjacent to the palatal surfaces of maxillary molars twice a week for 15 days. Matrix metalloproteinase-13 (Mmp-13) shRNA or a specific biochemical inhibitor were also injected into the same sites in alternating days with the LPS injections. Efficacy of shRNA-mediated silencing of Mmp-13 was verified by quantitative real-time polymerase chain reaction (qPCR) and immunoblot. Bone resorption was assessed by microcomputed tomography (uCT). Histological sections stained with hematoxylin/eosin (H/E) were used in the stereometric analysis of the inflammatory infiltrate. Gingival tissues were used to evaluate expression of Mmp-13, Il-6, Tnf-α, Ptgs2, and Rankl (qPCR). Protein levels of TGF-ß and IL-10 in the tissues were determined by enzyme-linked immunosorbent assays (ELISA) or by MMP-13 and p38 immunoblot. RESULTS: Silencing Mmp-13 expression reduced bone resorption significantly. Expression of Mmp-13, Il-6, and Tnf-α, as well as the protein levels of IL-6 and TNF-α, was reduced in the animals treated with adenovirus-delivered shRNA; however, these effects were not associated with modulation of p38 MAPK signaling. Interestingly, inhibition Mmp-13 did not affect the severity of inflammatory infiltrate. CONCLUSIONS: Site-specific inhibition of MMP-13 reduced bone resorption and production of inflammatory mediators associated with periodontal disease. CLINICAL RELEVANCE: The results suggest that site-specific inhibition of MMP-13 may be an interesting strategy to modulate inflammation and reduce bone resorption in osteolytic inflammatory diseases.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Doenças Periodontais / Reabsorção Óssea Tipo de estudo: Risk_factors_studies Limite: Animals Idioma: En Revista: Clin Oral Investig Assunto da revista: ODONTOLOGIA Ano de publicação: 2021 Tipo de documento: Article País de afiliação: Brasil País de publicação: Alemanha
Texto completo
Adicionar na Minha BVS
Imprimir
XML
PubMed Links
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Doenças Periodontais / Reabsorção Óssea Tipo de estudo: Risk_factors_studies Limite: Animals Idioma: En Revista: Clin Oral Investig Assunto da revista: ODONTOLOGIA Ano de publicação: 2021 Tipo de documento: Article País de afiliação: Brasil País de publicação: Alemanha