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Grape seed extracts inhibit dentin matrix degradation by MMP-3.

Khaddam M, Salmon B, Le Denmat D, Tjaderhane L, Menashi S, Chaussain C, Rochefort GY, Boukpessi T - Front Physiol (2014)

Bottom Line: Grape seed extracts (GSE) have been previously reported to be natural inhibitors of MMPs.Standardized blocks of dentin obtained from sound permanent teeth extracted for orthodontic reasons were demineralized with Ethylenediaminetetraacetic acid (EDTA) and pretreated either with (A) GSE (0.2% w/v), (B) amine fluoride (AmF) (20% w/v), (C) a mouthrinse which contains both, (D) placebo, (E) sodium fluoride (0.15 mg.ml(-1)), (F) PBS, (G) Chlorhexidine digluconate (CHX), or (H) zinc chloride (ZnCl2).However, the procedure should be adapted to clinically relevant durations.

View Article: PubMed Central - PubMed

Affiliation: EA 2496, Orofacial Pathologies, Imaging and Biotherapies, Dental school, University Paris Descartes, Sorbonne Paris Cité Montrouge, France.

ABSTRACT

Unlabelled: Since Matrix metalloproteinases (MMPs) have been suggested to contribute to dentin caries progression, the hypothesis that MMP inhibition would affect the progression of dentin caries is clinically relevant. Grape seed extracts (GSE) have been previously reported to be natural inhibitors of MMPs.

Objective: To evaluate the capacity of a GSE mouthrinse to prevent the degradation of demineralized dentin matrix by MMP-3 (stromelysin-1).

Materials and methods: Standardized blocks of dentin obtained from sound permanent teeth extracted for orthodontic reasons were demineralized with Ethylenediaminetetraacetic acid (EDTA) and pretreated either with (A) GSE (0.2% w/v), (B) amine fluoride (AmF) (20% w/v), (C) a mouthrinse which contains both, (D) placebo, (E) sodium fluoride (0.15 mg.ml(-1)), (F) PBS, (G) Chlorhexidine digluconate (CHX), or (H) zinc chloride (ZnCl2). The dentin blocks were then incubated with activated recombinant MMP-3. The supernatants were analyzed by Western Blot for several dentin matrix proteins known to be MMP-3 substrate. In parallel, scanning electron microscopy (SEM) was performed on resin replica of the dentin blocks.

Results: Western blot analysis of the supernatants revealed that MMP-3 released from the dentin matrix small proteoglycans (decorin and biglycan) and dentin sialoprotein (DSP) in the AmF, sodium fluoride, PBS and placebo pretreated groups, but not in the GSE and mouthrinse pretreated groups. SEM examination of resin replica showed that the mouthrinse and its active components not only had an anti-MMP action but also modified the dentin surface accessibility.

Conclusion: This study shows that GSE either alone or combined with AmF as in the evaluated mouthrinse limits dentin matrix degradation. This association may be promising to prevent the progression of caries within dentin. However, the procedure should be adapted to clinically relevant durations.

No MeSH data available.


Related in: MedlinePlus

Hypothetic representation of MMP-3 inhibition by the tested mouthrinse during the dentin carious process. Cariogenic bacteria present in the caries cavity release acids that demineralize the dentin matrix and activate host dentin or saliva-derived MMPs, including MMP-3. Activated MMP-3 then releases from the collagen scaffold several non-collagenous proteins (NCPs): DCN, BGN and some Sibling proteins. Mouthrinse, composed of GSE (Grape Seed Extracts) and AmF is an efficient MMP inhibitor that prevents the release of NCPs associated to the collagen fibers in the dentin.
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Figure 4: Hypothetic representation of MMP-3 inhibition by the tested mouthrinse during the dentin carious process. Cariogenic bacteria present in the caries cavity release acids that demineralize the dentin matrix and activate host dentin or saliva-derived MMPs, including MMP-3. Activated MMP-3 then releases from the collagen scaffold several non-collagenous proteins (NCPs): DCN, BGN and some Sibling proteins. Mouthrinse, composed of GSE (Grape Seed Extracts) and AmF is an efficient MMP inhibitor that prevents the release of NCPs associated to the collagen fibers in the dentin.

Mentions: Our results show that dentin pretreatment with the tested mouthrinse, and to some extent with its active principles, limits dentin matrix disorganization induced by MMP-3, especially along the dentinal tubules (Figure 4). In this study, we used an in vitro model combining a demineralization process and a subsequent MMP-3 treatment in order to test MMP inhibitors on dentin matrix degradation (Boukpessi et al., 2008). MMP-3 has been identified in predentin (Hall et al., 1999) and in dentin (Boukpessi et al., 2008), where it localizes within the intertubular dentin, along the collagen fibrils (Mazzoni et al., 2009). In vitro human demineralized dentin has been extensively used as a model to study the caries process (Ten Cate et al., 1991). However, demineralized dentin represents a simplified model of the caries process (Ten Cate, 2001), as it does not take into account the degradation of the organic matrix by endogenous proteinases and/or by bacterial collagenases. Therefore, the selected model would be more relevant to mimic dentin matrix degradation and to test the effect of MMP inhibitors.


Grape seed extracts inhibit dentin matrix degradation by MMP-3.

Khaddam M, Salmon B, Le Denmat D, Tjaderhane L, Menashi S, Chaussain C, Rochefort GY, Boukpessi T - Front Physiol (2014)

Hypothetic representation of MMP-3 inhibition by the tested mouthrinse during the dentin carious process. Cariogenic bacteria present in the caries cavity release acids that demineralize the dentin matrix and activate host dentin or saliva-derived MMPs, including MMP-3. Activated MMP-3 then releases from the collagen scaffold several non-collagenous proteins (NCPs): DCN, BGN and some Sibling proteins. Mouthrinse, composed of GSE (Grape Seed Extracts) and AmF is an efficient MMP inhibitor that prevents the release of NCPs associated to the collagen fibers in the dentin.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4215787&req=5

Figure 4: Hypothetic representation of MMP-3 inhibition by the tested mouthrinse during the dentin carious process. Cariogenic bacteria present in the caries cavity release acids that demineralize the dentin matrix and activate host dentin or saliva-derived MMPs, including MMP-3. Activated MMP-3 then releases from the collagen scaffold several non-collagenous proteins (NCPs): DCN, BGN and some Sibling proteins. Mouthrinse, composed of GSE (Grape Seed Extracts) and AmF is an efficient MMP inhibitor that prevents the release of NCPs associated to the collagen fibers in the dentin.
Mentions: Our results show that dentin pretreatment with the tested mouthrinse, and to some extent with its active principles, limits dentin matrix disorganization induced by MMP-3, especially along the dentinal tubules (Figure 4). In this study, we used an in vitro model combining a demineralization process and a subsequent MMP-3 treatment in order to test MMP inhibitors on dentin matrix degradation (Boukpessi et al., 2008). MMP-3 has been identified in predentin (Hall et al., 1999) and in dentin (Boukpessi et al., 2008), where it localizes within the intertubular dentin, along the collagen fibrils (Mazzoni et al., 2009). In vitro human demineralized dentin has been extensively used as a model to study the caries process (Ten Cate et al., 1991). However, demineralized dentin represents a simplified model of the caries process (Ten Cate, 2001), as it does not take into account the degradation of the organic matrix by endogenous proteinases and/or by bacterial collagenases. Therefore, the selected model would be more relevant to mimic dentin matrix degradation and to test the effect of MMP inhibitors.

Bottom Line: Grape seed extracts (GSE) have been previously reported to be natural inhibitors of MMPs.Standardized blocks of dentin obtained from sound permanent teeth extracted for orthodontic reasons were demineralized with Ethylenediaminetetraacetic acid (EDTA) and pretreated either with (A) GSE (0.2% w/v), (B) amine fluoride (AmF) (20% w/v), (C) a mouthrinse which contains both, (D) placebo, (E) sodium fluoride (0.15 mg.ml(-1)), (F) PBS, (G) Chlorhexidine digluconate (CHX), or (H) zinc chloride (ZnCl2).However, the procedure should be adapted to clinically relevant durations.

View Article: PubMed Central - PubMed

Affiliation: EA 2496, Orofacial Pathologies, Imaging and Biotherapies, Dental school, University Paris Descartes, Sorbonne Paris Cité Montrouge, France.

ABSTRACT

Unlabelled: Since Matrix metalloproteinases (MMPs) have been suggested to contribute to dentin caries progression, the hypothesis that MMP inhibition would affect the progression of dentin caries is clinically relevant. Grape seed extracts (GSE) have been previously reported to be natural inhibitors of MMPs.

Objective: To evaluate the capacity of a GSE mouthrinse to prevent the degradation of demineralized dentin matrix by MMP-3 (stromelysin-1).

Materials and methods: Standardized blocks of dentin obtained from sound permanent teeth extracted for orthodontic reasons were demineralized with Ethylenediaminetetraacetic acid (EDTA) and pretreated either with (A) GSE (0.2% w/v), (B) amine fluoride (AmF) (20% w/v), (C) a mouthrinse which contains both, (D) placebo, (E) sodium fluoride (0.15 mg.ml(-1)), (F) PBS, (G) Chlorhexidine digluconate (CHX), or (H) zinc chloride (ZnCl2). The dentin blocks were then incubated with activated recombinant MMP-3. The supernatants were analyzed by Western Blot for several dentin matrix proteins known to be MMP-3 substrate. In parallel, scanning electron microscopy (SEM) was performed on resin replica of the dentin blocks.

Results: Western blot analysis of the supernatants revealed that MMP-3 released from the dentin matrix small proteoglycans (decorin and biglycan) and dentin sialoprotein (DSP) in the AmF, sodium fluoride, PBS and placebo pretreated groups, but not in the GSE and mouthrinse pretreated groups. SEM examination of resin replica showed that the mouthrinse and its active components not only had an anti-MMP action but also modified the dentin surface accessibility.

Conclusion: This study shows that GSE either alone or combined with AmF as in the evaluated mouthrinse limits dentin matrix degradation. This association may be promising to prevent the progression of caries within dentin. However, the procedure should be adapted to clinically relevant durations.

No MeSH data available.


Related in: MedlinePlus