Silencing matrix metalloproteinase-13 (Mmp-13) reduces inflammatory bone resorption associated with LPS-induced periodon
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ORIGINAL ARTICLE
Silencing matrix metalloproteinase-13 (Mmp-13) reduces inflammatory bone resorption associated with LPS-induced periodontal disease in vivo Morgana R. Guimaraes-Stabili 1 & Marcell Costa de Medeiros 1 & Danuza Rossi 2 & Angelo Constantino Camilli 1 & Cleslei Fernando Zanelli 2 & Sandro Roberto Valentini 2 & Luis Carlos Spolidorio 3 & Keith Lough Kirkwood 4 & Carlos Rossa Jr 1 Received: 20 May 2020 / Accepted: 13 October 2020 # Springer-Verlag GmbH Germany, part of Springer Nature 2020
Abstract 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 shRNAmediated 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, Il6, 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. Keywords Metalloproteinase-13 . Lipopolysaccharide . Periodontal disease . Bone resorption . Inflammation Supplementary Information The online version contains supplementary material available at https://doi.org/10.1007/s00784-02003644-3. * Morgana R. Guimaraes-Stabili [email protected] 1
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
2
Department of Biological Sciences, School of Pharmaceutical Sciences, UNESP, Araraquara, SP, Brazil
3
Department of Physiology and Pathology, School of Dentistry at Araraquara, UNESP, Araraquara,
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