Silencing matrix metalloproteinase-13 (Mmp-13) reduces inflammatory bone resorption associated with LPS-induced periodontal disease in vivo

• Published in: Clinical oral investigations Vol. 25; no. 5; pp. 3161 - 3172
• Main Authors: 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
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01.05.2021; Springer Nature B.V
• Subjects: Animal models; Animals; Bone Resorption; Collagenase 3; Computed tomography; Dentistry; Enzyme-linked immunosorbent assay; Gum disease; Inflammation; Inflammatory diseases; Interleukin 10; Interleukin 6; Kinases; Lipopolysaccharides; MAP kinase; Matrix metalloproteinase; Matrix Metalloproteinase 13 - genetics; Medicine; Metalloproteinase; Mice; Molars; Original Article; Osteolysis; Periodontal Diseases; Periodontitis; Polymerase chain reaction; TRANCE protein; Tumor necrosis factor-α; X-Ray Microtomography; Bone resorption; Lipopolysaccharide; Periodontal disease; Inflammation; Metalloproteinase-13
• ISSN: 1432-6981; 1436-3771
• DOI: 10.1007/s00784-020-03644-3

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.