Silencing matrix metalloproteinase-13 (Mmp-13) reduces inflammatory bone resorption associated with LPS-induced periodontal disease in vivo
Autor(a) principal: | |
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Data de Publicação: | 2021 |
Outros Autores: | , , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da UNESP |
Texto Completo: | http://dx.doi.org/10.1007/s00784-020-03644-3 http://hdl.handle.net/11449/206770 |
Resumo: | 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-β 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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Silencing matrix metalloproteinase-13 (Mmp-13) reduces inflammatory bone resorption associated with LPS-induced periodontal disease in vivoBone resorptionInflammationLipopolysaccharideMetalloproteinase-13Periodontal diseaseObjectives: 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-β 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.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Department of Diagnosis and Surgery School of Dentistry at Araraquara-State University of São Paulo UNESP, Rua Humaita, 1680, CentroDepartment of Biological Sciences School of Pharmaceutical Sciences UNESPDepartment of Physiology and Pathology School of Dentistry at Araraquara UNESPDepartment of Oral Biology University at Buffalo State University of New YorkDepartment of Diagnosis and Surgery School of Dentistry at Araraquara-State University of São Paulo UNESP, Rua Humaita, 1680, CentroDepartment of Biological Sciences School of Pharmaceutical Sciences UNESPDepartment of Physiology and Pathology School of Dentistry at Araraquara UNESPFAPESP: 2007/05583-3Universidade Estadual Paulista (Unesp)State University of New YorkGuimaraes-Stabili, Morgana R. [UNESP]de Medeiros, Marcell Costa [UNESP]Rossi, Danuza [UNESP]Camilli, Angelo Constantino [UNESP]Zanelli, Cleslei Fernando [UNESP]Valentini, Sandro Roberto [UNESP]Spolidorio, Luis Carlos [UNESP]Kirkwood, Keith LoughRossa, Carlos [UNESP]2021-06-25T10:37:51Z2021-06-25T10:37:51Z2021-05-01info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/article3161-3172http://dx.doi.org/10.1007/s00784-020-03644-3Clinical Oral Investigations, v. 25, n. 5, p. 3161-3172, 2021.1436-37711432-6981http://hdl.handle.net/11449/20677010.1007/s00784-020-03644-32-s2.0-8509484163115256654089001950000-0001-7831-1149Scopusreponame:Repositório Institucional da UNESPinstname:Universidade Estadual Paulista (UNESP)instacron:UNESPengClinical Oral Investigationsinfo:eu-repo/semantics/openAccess2022-02-11T00:06:23Zoai:repositorio.unesp.br:11449/206770Repositório InstitucionalPUBhttp://repositorio.unesp.br/oai/requestopendoar:29462022-02-11T00:06:23Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)false |
dc.title.none.fl_str_mv |
Silencing matrix metalloproteinase-13 (Mmp-13) reduces inflammatory bone resorption associated with LPS-induced periodontal disease in vivo |
title |
Silencing matrix metalloproteinase-13 (Mmp-13) reduces inflammatory bone resorption associated with LPS-induced periodontal disease in vivo |
spellingShingle |
Silencing matrix metalloproteinase-13 (Mmp-13) reduces inflammatory bone resorption associated with LPS-induced periodontal disease in vivo Guimaraes-Stabili, Morgana R. [UNESP] Bone resorption Inflammation Lipopolysaccharide Metalloproteinase-13 Periodontal disease |
title_short |
Silencing matrix metalloproteinase-13 (Mmp-13) reduces inflammatory bone resorption associated with LPS-induced periodontal disease in vivo |
title_full |
Silencing matrix metalloproteinase-13 (Mmp-13) reduces inflammatory bone resorption associated with LPS-induced periodontal disease in vivo |
title_fullStr |
Silencing matrix metalloproteinase-13 (Mmp-13) reduces inflammatory bone resorption associated with LPS-induced periodontal disease in vivo |
title_full_unstemmed |
Silencing matrix metalloproteinase-13 (Mmp-13) reduces inflammatory bone resorption associated with LPS-induced periodontal disease in vivo |
title_sort |
Silencing matrix metalloproteinase-13 (Mmp-13) reduces inflammatory bone resorption associated with LPS-induced periodontal disease in vivo |
author |
Guimaraes-Stabili, Morgana R. [UNESP] |
author_facet |
Guimaraes-Stabili, Morgana R. [UNESP] de Medeiros, Marcell Costa [UNESP] Rossi, Danuza [UNESP] Camilli, Angelo Constantino [UNESP] Zanelli, Cleslei Fernando [UNESP] Valentini, Sandro Roberto [UNESP] Spolidorio, Luis Carlos [UNESP] Kirkwood, Keith Lough Rossa, Carlos [UNESP] |
author_role |
author |
author2 |
de Medeiros, Marcell Costa [UNESP] Rossi, Danuza [UNESP] Camilli, Angelo Constantino [UNESP] Zanelli, Cleslei Fernando [UNESP] Valentini, Sandro Roberto [UNESP] Spolidorio, Luis Carlos [UNESP] Kirkwood, Keith Lough Rossa, Carlos [UNESP] |
author2_role |
author author author author author author author author |
dc.contributor.none.fl_str_mv |
Universidade Estadual Paulista (Unesp) State University of New York |
dc.contributor.author.fl_str_mv |
Guimaraes-Stabili, Morgana R. [UNESP] de Medeiros, Marcell Costa [UNESP] Rossi, Danuza [UNESP] Camilli, Angelo Constantino [UNESP] Zanelli, Cleslei Fernando [UNESP] Valentini, Sandro Roberto [UNESP] Spolidorio, Luis Carlos [UNESP] Kirkwood, Keith Lough Rossa, Carlos [UNESP] |
dc.subject.por.fl_str_mv |
Bone resorption Inflammation Lipopolysaccharide Metalloproteinase-13 Periodontal disease |
topic |
Bone resorption Inflammation Lipopolysaccharide Metalloproteinase-13 Periodontal disease |
description |
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-β 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. |
publishDate |
2021 |
dc.date.none.fl_str_mv |
2021-06-25T10:37:51Z 2021-06-25T10:37:51Z 2021-05-01 |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://dx.doi.org/10.1007/s00784-020-03644-3 Clinical Oral Investigations, v. 25, n. 5, p. 3161-3172, 2021. 1436-3771 1432-6981 http://hdl.handle.net/11449/206770 10.1007/s00784-020-03644-3 2-s2.0-85094841631 1525665408900195 0000-0001-7831-1149 |
url |
http://dx.doi.org/10.1007/s00784-020-03644-3 http://hdl.handle.net/11449/206770 |
identifier_str_mv |
Clinical Oral Investigations, v. 25, n. 5, p. 3161-3172, 2021. 1436-3771 1432-6981 10.1007/s00784-020-03644-3 2-s2.0-85094841631 1525665408900195 0000-0001-7831-1149 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
Clinical Oral Investigations |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
3161-3172 |
dc.source.none.fl_str_mv |
Scopus reponame:Repositório Institucional da UNESP instname:Universidade Estadual Paulista (UNESP) instacron:UNESP |
instname_str |
Universidade Estadual Paulista (UNESP) |
instacron_str |
UNESP |
institution |
UNESP |
reponame_str |
Repositório Institucional da UNESP |
collection |
Repositório Institucional da UNESP |
repository.name.fl_str_mv |
Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP) |
repository.mail.fl_str_mv |
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1799964479051530240 |