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http://purl.uniprot.org/citations/33140162http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/33140162http://www.w3.org/2000/01/rdf-schema#comment"

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."xsd:string
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http://purl.uniprot.org/citations/33140162http://purl.uniprot.org/core/author"Rossi D."xsd:string
http://purl.uniprot.org/citations/33140162http://purl.uniprot.org/core/author"Valentini S.R."xsd:string
http://purl.uniprot.org/citations/33140162http://purl.uniprot.org/core/author"Zanelli C.F."xsd:string
http://purl.uniprot.org/citations/33140162http://purl.uniprot.org/core/author"Kirkwood K.L."xsd:string
http://purl.uniprot.org/citations/33140162http://purl.uniprot.org/core/author"Rossa C. Jr."xsd:string
http://purl.uniprot.org/citations/33140162http://purl.uniprot.org/core/author"Spolidorio L.C."xsd:string
http://purl.uniprot.org/citations/33140162http://purl.uniprot.org/core/author"de Medeiros M.C."xsd:string
http://purl.uniprot.org/citations/33140162http://purl.uniprot.org/core/author"Camilli A.C."xsd:string
http://purl.uniprot.org/citations/33140162http://purl.uniprot.org/core/author"Guimaraes-Stabili M.R."xsd:string
http://purl.uniprot.org/citations/33140162http://purl.uniprot.org/core/date"2021"xsd:gYear
http://purl.uniprot.org/citations/33140162http://purl.uniprot.org/core/name"Clin Oral Investig"xsd:string
http://purl.uniprot.org/citations/33140162http://purl.uniprot.org/core/pages"3161-3172"xsd:string
http://purl.uniprot.org/citations/33140162http://purl.uniprot.org/core/title"Silencing matrix metalloproteinase-13 (Mmp-13) reduces inflammatory bone resorption associated with LPS-induced periodontal disease in vivo."xsd:string
http://purl.uniprot.org/citations/33140162http://purl.uniprot.org/core/volume"25"xsd:string
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