The Role of Matrix Metalloproteinases in Periodontal Disease

Checchi, Vittorio; Maravić, Tatjana; Bellini, Pierantonio; Generali, Luigi; Consolo, Ugo; Breschi, Lorenzo; Mazzoni, Annalisa

doi:10.3390/ijerph17144923

Cited by 108 publications

(125 citation statements)

References 82 publications

(112 reference statements)

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“…In addition to the action of proteases produced by P . gingivalis , matrix metalloproteinases secreted by resident and immune cells also participate in this process [ 40 ]. We are currently investigating whether the tart cherry extract is also effective in inhibiting the catalytic activity of matrix metalloproteinases.…”

Section: Discussionmentioning

confidence: 99%

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Effects of a tart cherry (Prunus cerasus L.) phenolic extract on Porphyromonas gingivalis and its ability to impair the oral epithelial barrier

et al. 2021

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Periodontal diseases, including gingivitis and periodontitis, are a global oral health problem. Porphyromonas gingivalis, a key pathogen involved in the onset of periodontitis, is able to colonize the subgingival epithelium and invade the underlying connective tissue due to the contribution of cysteine proteases known as gingipains. In this study, we investigated the effects of a phenolic extract prepared from tart cherry (Prunus cerasus L.) juice on the growth, adherence, and protease activity of P. gingivalis. We also assessed the protective effect of the tart cherry extract on the disruption of the oral epithelial barrier induced by P. gingivalis. The tart cherry extract that contains procyanidins and quercetin and its derivatives (rutinoside, glucoside) as the most important phenolic compounds attenuated P. gingivalis growth, reduced adherence to an experimental basement membrane matrix model, and decreased the protease activities of P. gingivalis. The tart cherry extract also exerted a protective effect on the integrity of the oral epithelial barrier in an in vitro model infected with P. gingivalis. More specifically, the extract prevented a decrease in transepithelial electrical resistance as well as the destruction of tight junction proteins (zonula occludens-1 and occludin). These results suggest that the tart cherry phenolic extract may be a promising natural product for the treatment of periodontitis through its ability to attenuate the virulence properties of P. gingivalis and curtail the ability of this pathogen to impair the oral epithelial barrier.

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Section: Discussionmentioning

confidence: 99%

“…this process [40]. We are currently investigating whether the tart cherry extract is also effective in inhibiting the catalytic activity of matrix metalloproteinases.…”

Section: Plos Onementioning

confidence: 99%

Effects of a tart cherry (Prunus cerasus L.) phenolic extract on Porphyromonas gingivalis and its ability to impair the oral epithelial barrier

et al. 2021

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“…While most collagen is degraded by collagenases such as MMP-1, MMP-8 and MMP-13, MMP-2 is the predominately expressed species in human PDLs and has been shown to diffuse and actively degrade fibrillar collagen (83). MMP proteolytic cascades can also lead to widespread periodontal tissue destruction due to cooperative MMP activation (97). Although has no direct role in degrading collagen, it is a potent activator of pro-enzymatic MMP-2(97).…”

Section: The Main Enzymes Responsible For Catabolic Breakdown Of Collmentioning

confidence: 99%

Treponema denticoladentilisin triggered TLR2/MyD88 activation upregulates a tissue destructive program involving MMPs via Sp1 in human oral cells

Ganther

Radaic

Chang

et al. 2021

Preprint

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Periodontal disease is driven by dysbiosis of the oral microbiome, resulting in over-representation of species that induce the release of pro-inflammatory cytokines, chemokines, and tissue-remodeling matrix metalloproteinases (MMPs) in the periodontium. These chronic tissue-destructive inflammatory responses result in gradual loss of tooth-supporting alveolar bone. The oral spirochete Treponema denticola, is consistently found at significantly elevated levels in periodontal lesions. Host-expressed Toll-Like Receptor 2 (TLR2) senses a variety of bacterial ligands, including acylated lipopolysaccharides and lipoproteins. T. denticola dentilisin, a surface-expressed protease complex comprised of three lipoproteins has been implicated as a virulence factor in periodontal disease, primarily due to its proteolytic activity. While the role of acylated bacterial components in induction of inflammation is well-studied, little attention has been given to the potential role of the acylated nature of dentilisin. The purpose of this study was to test the hypothesis that T. denticola dentilisin activates a TLR2-dependent mechanism, leading to upregulation of tissue-destructive genes in periodontal tissue. RNA-sequencing of periodontal ligament cells challenged with T. denticola bacteria revealed a significant upregulation of genes associated with extracellular matrix organization and degradation, including tissue-specific inducible MMPs that may play novel roles in modulating host immune responses yet to be characterized within the context of oral disease. The Gram-negative oral commensal, Veillonella parvula, failed to upregulate these same MMPs. Dentilisin-induced upregulation of MMPs was mediated via TLR2 and MyD88 activation, since knockdown of either TLR2 or MyD88 abrogated these effects. Challenge with purified dentilisin upregulated the same MMPs, whereas a dentilisin-deficient T. denticola mutant had no effect. Finally, T. denticola-mediated activation of TLR2/MyD88 led to the nuclear translocation of the transcription factor Sp1, which was shown to be a critical regulator of all T. denticola-dependent MMP expression. Taken together, these data support that T. denticola dentilisin stimulates tissue-destructive cellular processes in a TLR2/MyD88/Sp1-dependent fashion.AUTHOR SUMMARYPeriodontal disease is driven by dysbiosis of the oral microbiome, which interacts with host tissues and thereby induces the release of pro-inflammatory cytokines, chemokines, and tissue-remodeling matrix metalloproteinases (MMPs), leading to destruction of the periodontal tissues. Even after clinical intervention, patients with severe periodontal disease are left with a persistent pro-inflammatory transcriptional profile throughout the periodontium. The oral spirochete, Treponema denticola, is consistently found at elevated levels in periodontal lesions and is associated with several pathophysiological effects driving periodontal disease progression. The T. denticola surface-expressed protease complex (dentilisin) has cytopathic effects consistent with periodontal disease pathogenesis. To date, few direct links have been reported between dentilisin and the cellular and tissue processes that drive periodontal tissue destruction at the transcriptional and/or epigenetic levels. Here, we utilize wild type and dentilisin-deficient T. denticola as well as purified dentilisin to characterize dentilisin-dependent activation of intracellular pathways controlling MMP expression and activity. Our results define a role for dentilisin in initiating this signal cascade. Also, our study identified tissue-specific inducible MMPs that may play novel roles in modulating as-yet uncharacterized host responses in periodontal disease. Lastly, T. denticola dentilisin stimulates tissue-destructive cellular processes in a TLR2/MyD88/Sp1-dependent fashion. Taken together, our study provides new insights into the molecular mechanisms underpinning periodontal disease progression which could lead to the development of more efficacious therapeutic treatments.

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“… 8 MMP9 is associated with periodontitis 9 and the level of MMP9 increases with the severity of the disease. 10 …”

Section: Introductionmentioning

confidence: 99%

Evaluation of the efficacy of lycopene gel compared with minocycline hydrochloride microspheres as an adjunct to nonsurgical periodontal treatment: A randomised clinical trial

Ali

Saliem

Abdulkareem

et al. 2021

Journal of Dental Sciences

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Background/purpose The prescription of antibiotics as an adjunct to mechanical periodontal therapy in patients with severe periodontitis is recommended; however, the side effects of antibiotics are a major concern. The aim of this study was to evaluate the efficacy of lycopene (Lyc) antioxidant gel versus minocycline hydrochloride microspheres (ARISTIN) as an adjunct to the nonsurgical treatment of periodontitis. Materials and methods Three identical periodontal pockets/patient received root surface debridement followed by the random application of either ARISTIN, Lyc, or placebo gel (control, Ctrl). Clinical parameters, plaque index, bleeding on probing, probing pocket depth, and clinical attachment loss, were recorded at the baseline and after 30 days. Additionally, the levels of interleukin-8 (IL-8), matrix metallopeptidase 9, and tissue inhibitor of metalloproteinases 1 (TIMP1) in gingival crevicular fluid samples were assessed at the same time points. Results Twenty-three patients with periodontitis completed the study. Both ARISTIN and Lyc treatments showed significantly greater gains in attachment (1.94 ± 1.33 and 1.72 ± 0.88, respectively) than the Ctrl treatment (1.04 ± 0.96). Compared with those in the Ctrl, only ARISTIN showed a significant reduction in IL-8 level, whereas TIMP1 levels were significantly upregulated in the Lyc gel and ARISTIN sites. The effect size estimation indicated that Lyc gel exhibited considerably greater efficacy than the Ctrl gel. Conclusion Lyc gel and ARISTIN offer almost equal improvement in both clinical and biochemical parameters of periodontitis.

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The Role of Matrix Metalloproteinases in Periodontal Disease

Cited by 108 publications

References 82 publications

Effects of a tart cherry (Prunus cerasus L.) phenolic extract on Porphyromonas gingivalis and its ability to impair the oral epithelial barrier

Effects of a tart cherry (Prunus cerasus L.) phenolic extract on Porphyromonas gingivalis and its ability to impair the oral epithelial barrier

Treponema denticoladentilisin triggered TLR2/MyD88 activation upregulates a tissue destructive program involving MMPs via Sp1 in human oral cells

Evaluation of the efficacy of lycopene gel compared with minocycline hydrochloride microspheres as an adjunct to nonsurgical periodontal treatment: A randomised clinical trial

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