The Expression of Macrophage and Neutrophil Elastases in Rat Periradicular Lesions

Morimoto, Tetsuya; Yamasaki, Masahiro; Nakata, Kohei; Tsuji, Masaaki; Nakamura, Hiroshi

doi:10.1016/j.joen.2008.06.012

Cited by 16 publications

(10 citation statements)

References 33 publications

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“…Of these, 6t proved to be the more potent and the less toxic in cell and tissue culture and in in vivo studies. It is significant that MMP-12 is produced by osteoclasts [42] and its inhibition (as described in the current study) by 6t at least partially explains the ability of this compound (together with inhibition of other MMPs such as MMP-13) to prevent bone-destruction in the diabetic rats. Compound 6s was not pursued further because, (a) unlike 6t, it did not reduce diabetic complications in the rat in vivo (data not shown), and (b) it was less effective in reducing cartilage destruction in tissue culture [45].…”

Section: Discussionsupporting

confidence: 50%

Design, Synthesis and Biological Activity of New Polyenolic Inhibitors of Matrix Metalloproteinases: A Focus on Chemically-Modified Curcumins

Zhang

Gu²,

Lee³

et al. 2012

CMC

103

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Matrix metalloproteinases (MMPs) are essential for the degradation and turnover of components of the extracellular matrix (ECM) and, when pathologically elevated, mediate connective tissue loss (including bone destruction) in various inflammatory and other diseases. Tetracyclines (TCs) are known inhibitors of mammalian-derived MMPs, and non-antibiotic formulations of Doxycycline are FDA-approved to treat periodontitis and the chronic inflammatory skin disease, rosacea. Because the C-11/ C-12 diketonic moiety of the tetracyclines is primarily responsible, through zinc-binding, for MMP inhibition, we have uniquely modified curcumin as a "core" molecule, since it contains a similar enolic system and is known to have beneficial effects in diseases where connective-tissue loss occurs. Specifically we have developed new congeners which exhibit improved zinc-binding and solubility, and potent reduction of excessive MMP levels and activity. We now describe a series of curcuminoid bi- and tri-carbonylmethanes in which all of these properties are substantially improved. An N-phenylaminocarbonyl derivative of bis-demethoxycurcumin (CMC2.24) was selected as the "lead" substance because it showed superior potency in vitro (i.e., the lowest IC(50)) against a series of neutral proteases (MMPs) associated with tissue erosion. Moreover, CMC2.24 administered to diabetic rats orally (30mg/kg), reduced the secretion of pathologically-excessive levels of MMP-9 to normal in cultured peritoneal macrophages with no evidence of toxicity. Thus, this (and other similar novel) compound(s) may be useful in various diseases of connective-tissue loss.

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Section: Discussionsupporting

confidence: 50%

Design, Synthesis and Biological Activity of New Polyenolic Inhibitors of Matrix Metalloproteinases: A Focus on Chemically-Modified Curcumins

Zhang

Gu²,

Lee³

et al. 2012

CMC

103

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“…The process of periapical lesion formation in rat molars can be divided into the initial, acute and chronic phases (Morimoto et al 2008). In previous reports, during the initial phase of rat periapical lesions, inflammatory cells, including macrophages, were detected in the periapical tissue, and the accumulation of macrophages reached its highest level prior to pulp necrosis (Suzuki et al 1999).…”

Section: Discussionmentioning

confidence: 98%

“…The process of periapical lesion formation in rat molars can be divided into the initial, acute and chronic phases (Morimoto et al. 2008).…”

Section: Discussionmentioning

confidence: 99%

Expression of MMP-8 and MMP-13 in the development of periradicular lesions

Matsui

Yamasaki

Nakata

et al. 2011

International Endodontic Journal

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“…MMPs are a family of metal-dependent endopeptidases, which are secreted as inactive proenzymes (zymogens) and activated in tissues by cleavage of the propeptide (19–23). Although MMPs have been reported in periapical lesions (11, 24–30), a direct comparison of MMPs in cysts and granulomas has not been undertaken. Since MMPs must be activated to exert their function, it is also important to localize areas of proteinase activity within lesions.…”

Section: Introductionmentioning

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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The Expression of Macrophage and Neutrophil Elastases in Rat Periradicular Lesions

Cited by 16 publications

References 33 publications

Design, Synthesis and Biological Activity of New Polyenolic Inhibitors of Matrix Metalloproteinases: A Focus on Chemically-Modified Curcumins

Design, Synthesis and Biological Activity of New Polyenolic Inhibitors of Matrix Metalloproteinases: A Focus on Chemically-Modified Curcumins

Expression of MMP-8 and MMP-13 in the development of periradicular lesions

High Matrix Metalloproteinase Activity Is a Hallmark of Periapical Granulomas

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