The effect of chemical inhibition of matrix metalloproteinases on the size of experimentally induced apical periodontitis

Tjäderhane, Leo; Hotakainen, Tiina; Kinnunen, Sini; Ahonen, M.; Salo, Tuula

doi:10.1111/j.0143-2885.2007.01223.x

Cited by 27 publications

(24 citation statements)

References 36 publications

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“…Taken together, these findings indicate that specific MMPs are produced in different cell types in periapical lesions, suggesting specific roles for these enzymes in periapical disease pathogenesis. Indeed, recent reports have demonstrated distinct roles for MMPs in periapical disease progression, either stimulating (40) or attenuating lesion development (41). These data and our current findings underscore the importance of characterizing the profile of MMPs involved in periapical lesions prior to using pan-MMP inhibitors therapeutically that can non-specifically inhibit MMPs (23).…”

Section: Discussionmentioning

confidence: 99%

High Matrix Metalloproteinase Activity Is a Hallmark of Periapical Granulomas

Paula-Silva

D’Silva

Silva

et al. 2009

Journal of Endodontics

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Introduction Inability to distinguish periapical cysts from granulomas prior to performing root canal treatment leads to uncertainty in treatment outcomes, because cysts have lower healing rates. Searching for differential expression of molecules within cysts or granulomas could provide information with regard to the identity of the lesion or suggest mechanistic differences that may form the basis for future therapeutic intervention. Thus, we investigated whether granulomas and cysts exhibit differential expression of extracellular matrix (ECM) molecules. Methods Human periapical granulomas, periapical cysts, and healthy periodontal ligament tissues were used to investigate the differential expression of ECM molecules by microarray analysis. Since matrix metalloproteinases (MMP) showed the highest differential expression in the microarray analysis, MMPs were further examined by in situ zymography and immunohistochemistry. Data were analyzed using one-way ANOVA followed by Tukey test. Results We observed that cysts and granulomas differentially expressed several ECM molecules, especially those from the matrix metalloproteinase (MMP) family. Compared to cysts, granulomas exhibited higher MMP enzymatic activity in areas stained for MMP-9. These areas were composed of polymorphonuclear cells (PMNs), in contrast to cysts. Similarly, MMP-13 was expressed by a greater number of cells in granulomas compared to cysts. Conclusion Our findings indicate that high enzymatic MMP activity in PMNs together with MMP-9 and MMP-13 stained cells could be a molecular signature of granulomas, unlike periapical cysts.

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Section: Discussionmentioning

confidence: 99%

High Matrix Metalloproteinase Activity Is a Hallmark of Periapical Granulomas

Paula-Silva

D’Silva

Silva

et al. 2009

Journal of Endodontics

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“…Others have shown that polyvinylphosphonic acid (Tezvergil-Mutluay et al ., 2010b) and benzalkonium chloride (Pashley, unpublished observations) also possess generic anti-MMP activities. Chemically modified tetracyclines ( i.e ., tetracyclines that lack antibiotic activities but retain their anti-MMP activities) are effective non-specific MMP inhibitors and have been used as MMP inhibitors in experimental caries (Sulkala et al ., 2001) and periodontal disease models (Tjäderhane et al ., 2007). They have not been used to prevent the degradation of hybrid layers, since they may stain teeth with a purple hue after photo-oxidation of the tetracycline.…”

Section: Experimental Strategies To Prevent Degradation Of Resin-dentmentioning

confidence: 99%

Limitations in Bonding to Dentin and Experimental Strategies to Prevent Bond Degradation

et al. 2011

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The limited durability of resin-dentin bonds severely compromises the lifetime of tooth-colored restorations. Bond degradation occurs via hydrolysis of suboptimally polymerized hydrophilic resin components and degradation of water-rich, resin-sparse collagen matrices by matrix metalloproteinases (MMPs) and cysteine cathepsins. This review examined data generated over the past three years on five experimental strategies developed by different research groups for extending the longevity of resin-dentin bonds. They include: (1) increasing the degree of conversion and esterase resistance of hydrophilic adhesives; (2) the use of broad-spectrum inhibitors of collagenolytic enzymes, including novel inhibitor functional groups grafted to methacrylate resins monomers to produce anti-MMP adhesives; (3) the use of cross-linking agents for silencing the activities of MMP and cathepsins that irreversibly alter the 3-D structures of their catalytic/allosteric domains; (4) ethanol wet-bonding with hydrophobic resins to completely replace water from the extrafibrillar and intrafibrillar collagen compartments and immobilize the collagenolytic enzymes; and (5) biomimetic remineralization of the water-filled collagen matrix using analogs of matrix proteins to progressively replace water with intrafibrillar and extrafibrillar apatites to exclude exogenous collagenolytic enzymes and fossilize endogenous collagenolytic enzymes. A combination of several of these strategies should result in overcoming the critical barriers to progress currently encountered in dentin bonding.

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“…Se requieren nuevas investigaciones para establecer el rol de ellas y su interacción con los demás mediadores inflamatorios presentes. Recientemente, se ha descrito que las MMPs podrían actuar de manera protectora, inhibiendo la progresión de la destrucción de tejido periapical inducido por bacterias, como se ha reportado previamente en periodontitis crónica y apical (47) . Se ha observado que, en inflamación pulpar y periapical, contrariamente a lo esperado, la inhibición general de la actividad de las MMPs aumenta la propagación de la necrosis pulpar y la tasa de crecimiento de las LPAs, indicando que las MMPs pueden tener propiedades antiinfecciosas y/o antiinflamatorias desconocidas anteriormente (47) .…”

Section: Discussionunclassified

Inmunodetección de metaloproteinasas de matriz extracelular (MMPs)-2, -9, -13 y -14 en lesiones apicales asociadas con periodontitis apical asintomática

Burgos

Piwonka

Alfaro

et al. 2011

Rev. Clin. Periodoncia Implantol. Rehabil. Oral

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Inmunodetección de metaloproteinasas de matriz extracelular (MMPs)-2, -9, -13 y -14 en lesiones apicales asociadas con periodontitis apical asintomáticaImmunodetection of matrix metalloproteinases (MMPs)-2, -9, -13 and -14 in periapical lesions associated with asymptomatic apical periodontitis RESUMENLa periodontitis apical asintomática (PAa) es una patología infecciosa caracterizada por destrucción ósea perirradicular asociada a un proceso inflamatorio crónico y producción de mediadores inflamatorios, entre los cuales se encuentran las metaloproteinasas de matriz extracelular (MMPs).Entre éstas, las MMPs-13, -14, -2 y -9, son producidas por el tejido óseo y degradan sinérgicamente el colágeno tipo I, principal componente de los tejidos periodontales, y gelatina, producto de la degradación y desnaturación del colágeno. El objetivo de este estudio fue determinar el patrón de expresión de las MMPs-2, -9, -13 y -14 en granulomas periapicales (GPAs), quistes radiculares inflamatorios (QRIs) y ligamento periodontal sano (LS). Materiales y Métodos:Se seleccionaron 12 pacientes con diagnóstico clínico de PAa e indicación de exodoncia a partir de los cuales se obtuvieron biopsias de lesiones periapicales (LPAs). Como controles, se seleccionaron 7 individuos con indicación de exodoncia de premolares por ortodoncia, obteniéndose biopsias de LS. Se efectuó el diagnóstico anátomo-patológico de los especímenes y se caracterizó la expresión de las MMPs en estudio mediante inmunohistoquímica. Resultados: Las MMPs en estudio sólo se detectaron en GPAs y QRIs, y se inmunolocalizaron principalmente en el infiltrado inflamatorio de éstos. Adicionalmente, la MMP-2 se identificó en fibroblastos del tejido conectivo. Conclusiones: MMPs-2, -9, -13 y -14 se expresan predominantemente en el infiltrado inflamatorio de las LPAs y no en LS, y por tanto se sugiere la participación de estos mediadores en la patogénesis de la PAa. Rev. Clin. Periodoncia Implantol. Rehabil. Oral Vol. 4(1); 17-21, 2011.Palabras clave: Periodontitis apical asintomática, lesiones periapicales, metaloproteinasas de matriz extracelular. ABSTRACTAsymptomatic apical periodontitis (aAP) is an infectious disease characterized by perirradicular bone destruction associated with chronic inflammation and release of inflammatory mediators, such as matrix metalloproteinases (MMPs). MMPs-13, -14 and -2, -9 are bone-expressed enzymes that can synergistically degrade collagen I, the main component of periodontal extracellular matrix, and gelatin, the product of degradation and denaturation of collagen. The aim of this study was to characterize the expression pattern of MMPs-2, -9, -13, and -14 in periapical granulomas (PGs), radicular cysts (RCs) and healthy periodontal ligament (PDL). Materials and Methods: Individuals with clinical diagnosis of aAP and indication of extraction were selected (N=12), and biopsies of periapical lesions (PLs) were obtained. For controls, 7 subjects with indication of premolar extraction for orthodontic reasons were selected, and PDL biopsies wer...

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The effect of chemical inhibition of matrix metalloproteinases on the size of experimentally induced apical periodontitis

Abstract: MMP inhibition affects pulpal and periapical inflammation, increasing the rate of spreading of necrosis in root canals and the rate of periapical lesion formation.

Cited by 27 publications

References 36 publications

High Matrix Metalloproteinase Activity Is a Hallmark of Periapical Granulomas

High Matrix Metalloproteinase Activity Is a Hallmark of Periapical Granulomas

Limitations in Bonding to Dentin and Experimental Strategies to Prevent Bond Degradation

Inmunodetección de metaloproteinasas de matriz extracelular (MMPs)-2, -9, -13 y -14 en lesiones apicales asociadas con periodontitis apical asintomática

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