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Journal ArticleDOI

Zinc Inhibits Collagenolysis by Cathepsin K and Matrix Metalloproteinases in Demineralized Dentin Matrix.

01 Jan 2017-Caries Research (S. Karger AG)-Vol. 51, Iss: 6, pp 576-581
TL;DR: Cathepsin K-induced dentin collagen degradation can be strongly inhibited by zinc, and zinc levels of ≥5 mM can be considered as a reliable threshold for the stabilization of dentin matrices.
Abstract: The enzymatic degradation of dentin organic matrix occurs via both the action of matrix metalloproteinases (MMPs) and cysteine cathepsins (CCs). Zinc can prevent collagen hydrolysis by MMPs. However, its effect on the activity of dentin-bound CCs is not known. The aim of this study was to investigate the effect of zinc on matrix-bound cathepsin K and MMP activity in dentin. Completely demineralized dentin beams were divided into test groups (n = 9) and incubated at 37°C in an incubation media (1 mL) containing ZnCl2 of 0.02 (physiological level, control), 0.2, 0.5, 1, 5, 10, 20, 30, or 40 mM. The dry mass changes of the beams were determined, and incubation media were analyzed for cathepsin K- and MMP-specific collagen degradation end products - CTX (C-terminal cross-linked telopeptide of type I collagen) and ICTP (cross-linked carboxy-terminal telopeptide of type I collagen) - at 1, 3, and 7 days of incubation. The mass loss of the beams decreased when the zinc level in the incubation media was ≥5 mM (p < 0.05). The release of liberated collagen degradation telopeptides decreased in accordance with the decrease in the mass loss rates of the beams. Cathepsin K-induced dentin collagen degradation can be strongly inhibited by zinc. Zinc levels of ≥5 mM can be considered as a reliable threshold for the stabilization of dentin matrices.
Citations
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Journal ArticleDOI
TL;DR: Inhibition of MMPs using SnCl2 and SnF2 could play an important role in the prevention of dental erosion and caries, and the clinical relevance of these findings needs to be proven.

21 citations

Journal ArticleDOI
TL;DR: The inhibitory or stimulatory effect of Zn on MMPs seems to depend on physiological conditions of the cells or animals used, dose ofZn used, and duration of treatment.

18 citations

Journal ArticleDOI
TL;DR: An experimental three/two-step E&R/SE Exp_2UA combines high bonding potential and bond-degradation resistance with long-term ion release rendering the adhesive anti-enzymatic and anti-bacterial potential.
Abstract: Apart from producing high bond strength to tooth enamel and dentin, a dental adhesive with biotherapeutic potential is clinically desirable, aiming to further improve tooth restoration longevity. In this laboratory study, an experimental two-step universal adhesive, referred to as Exp_2UA, applicable in both the etch-and-rinse (E&R) and self-etch (SE) modes and combining a primer, containing 10-methacryloyloxydecyldihydrogen phosphate as a functional monomer with chemical binding potential to hydroxyapatite, with a bioglass-containing hydrophobic adhesive resin, was multifactorially investigated. In addition to primary property assessment, including measurement of bond strength, water sorption, solubility, and polymerization efficiency, the resultant adhesive-dentin interface was characterized by transmission electron microscopy (TEM), the filler composition was analyzed by energy-dispersive X-ray spectroscopy, and the bioactive potential of the adhesive was estimated by measuring the long-term ion release and assessing its antienzymatic and antibacterial potential. Four representative commercial adhesives were used as reference/controls. Application in both the E&R and SE modes resulted in a durable bonding performance to dentin, as evidenced by favorable 1 year aged bond strength data and a tight interfacial ultrastructure that, as examined by TEM, remained ultramorphologically unaltered upon 1 year of water storage aging. TEM revealed a 20 μm thick hydrophobic adhesive layer with a homogeneous bioglass filler distribution. Adequate polymerization conversion resulted in extremely low water sorption and solubility. In situ zymography revealed reduced endogenous proteolytic activity, while Streptococcus mutans biofilm formation was inhibited. In conclusion, the three-/two-step E&R/SE Exp_2UA combines the high bonding potential and bond degradation resistance with long-term ion release, rendering the adhesive antienzymatic and antibacterial potential.

15 citations

Journal ArticleDOI
TL;DR: In this in vitro study, cross-linking agents were applied with a fluoride regimen, which improved its treatment efficacy of root caries regarding the distribution of ion uptake and recovery of dentine biomechanics.

14 citations

Journal ArticleDOI
TL;DR: The novel prime-&-rinse mode using 5%M DP-BAC, 15%MDP and 15% MDP+MMPs inhibitors could significantly increase the short- and long-term dentin MTBS of self-etch adhesive, and might be a supplement to contemporary dentin bonding strategies.
Abstract: Objectives The study investigated the effects of novel prime-&-rinse mode using MDP (10-methacryloyloxydecyl dihydrogenphosphate) and matrix metalloproteinase (MMPs) inhibitors on dentin microtensile bond strengths (MTBS) of self-etch adhesive, resin-dentin interface degradations, and activity of recombinant human (rh) MMP-8, -9. Materials and methods Eight experimental primers were prepared using 5% and 15% of MDP ethanol-aqueous (1:1) solution in combination with/without MMPs inhibitors (1%benzalkonium chloride (BAC), 1000 μm/mL polyvinylphosphonic acid (PVPA) and 15%proanthocyanidin (PA)). Ninety human mid-coronal dentin surfaces were applied with the experimental primers, water-sprayed and gently air-dried (prime-&-rinse mode), or not (control, self-etch mode). The specimens were bonded with self-etch adhesive (Clearfil S3 Bond) and composite resin (Clearfil Majesty). The resin-bonded specimens were prepared into multiple micro-beams for MTBS tests after 24 h and 1 yr of water storage. The resin-dentin interfaces were analyzed with SEM/TEM. The inhibitory effects of eight primers on rhMMP-8, 9 were determined. The data were analyzed using two-way ANOVA and LSD multiple comparisons tests. Results Compared with control, all the primers used in prime-&-rinse mode could significantly improve long-term dentin MTBS (P Conclusions The novel prime-&-rinse mode using 5%MDP-BAC, 15%MDP and 15%MDP+MMPs inhibitors could significantly increase the short- and long-term dentin MTBS of self-etch adhesive. This might be a supplement to contemporary dentin bonding strategies.

10 citations

References
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Journal ArticleDOI
TL;DR: Observations support the view that the cysteine-switch mechanism is applicable to all members of this gene family and offers the opportunity for multiple modes of physiological activation of these important enzymes.
Abstract: The general applicability of the "cysteine-switch" activation mechanism to the members of the matrix metalloproteinase (MMP) gene family is examined here. All currently known members of the MMP gene family share the characteristic that they are synthesized in a latent, inactive, form. Recent evidence suggests that this latency in human fibroblast collagenase (HFC) is the result of formation of an intramolecular complex between the single cysteine residue in its propeptide domain and the essential zinc atom in the catalytic domain, a complex that blocks the active site. Latent HFC can be activated by multiple means, all of which effect the dissociation of the cysteine residue from the complex. This is referred to as the "cysteine-switch" mechanism of activation. The propeptide domain that contains the critical cysteine residue and the catalytic domain that contains the zinc-binding site are the only two domains common to all of the MMPs. The amino acid sequences surrounding both the critical cysteine residue and a region of the protein chains containing two of the putative histidine zinc-binding ligands are highly conserved in all of the MMPs. A survey of the literature shows that many of the individual MMPs can be activated by the multiple means observed for latent HFC. These observations support the view that the cysteine-switch mechanism is applicable to all members of this gene family. This mechanism is unprecedented in enzymology as far as we know and offers the opportunity for multiple modes of physiological activation of these important enzymes. Since conditions in different cells and tissues may match those necessary to effect one of these activation modes for a given MMP, this may offer metabolic flexibility in the control of MMP activation.

1,436 citations

Journal ArticleDOI
TL;DR: It is shown that the activity of cathepsin K alone is sufficient to dissolve completely insoluble collagen of adult human cortical bone and is likely to be responsible for the key role of cat hepsIn K in bone resorption.

621 citations


"Zinc Inhibits Collagenolysis by Cat..." refers background or methods in this paper

  • ...They also measured CTX fragments and showed that this was due only to cathepsin K activity in the bone [Garnero et al., 1998]....

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  • ...…namely CTX (C-terminal cross-linked telopeptide of type I collagen) and ICTP (cross-linked carboxy-terminal telopeptide of type I collagen), into the incubation media was used as an indirect measure of collagen breakdown due to cathepsin K and MMPs, respectively [Garnero et al., 1998, 2003]....

    [...]

Journal ArticleDOI
TL;DR: This review addresses recent findings regarding Zn signaling and its role in physiological processes and pathogenesis and proposes that intracellular ZN signaling falls into two classes, early and late Zn signaled.
Abstract: The essential trace element zinc (Zn) is widely required in cellular functions, and abnormal Zn homeostasis causes a variety of health problems that include growth retardation, immunodeficiency, hypogonadism, and neuronal and sensory dysfunctions. Zn homeostasis is regulated through Zn transporters, permeable channels, and metallothioneins. Recent studies highlight Zn’s dynamic activity and its role as a signaling mediator. Zn acts as an intracellular signaling molecule, capable of communicating between cells, converting extracellular stimuli to intracellular signals, and controlling intracellular events. We have proposed that intracellular Zn signaling falls into two classes, early and late Zn signaling. This review addresses recent findings regarding Zn signaling and its role in physiological processes and pathogenesis.

486 citations

Journal ArticleDOI
TL;DR: It is presented the case that the organic matrix in caries-affected dentin may not be preserved as intact as previously considered, and this would seriously compromise the matrix ability for intrafibrillar remineralization, which is considered essential in restoring the dentin's mechanical properties.
Abstract: Dentin organic matrix, with type I collagen as the main component, is exposed after demineralization in dentinal caries, erosion or acidic conditioning during adhesive composite restorative treatment. This exposed matrix is prone to slow hydrolytic degradation by host collagenolytic enzymes, matrix metalloproteinases (MMPs) and cysteine cathepsins. Here we review the recent findings demonstrating that inhibition of salivary or dentin endogenous collagenolytic enzymes may provide preventive means against progression of caries or erosion, just as they have been shown to retain the integrity and improve the longevity of resin composite filling bonding to dentin. This paper also presents the case that the organic matrix in caries-affected dentin may not be preserved as intact as previously considered. In partially demineralized dentin, MMPs and cysteine cathepsins with the ability to cleave off the terminal non-helical ends of collagen molecules (telopeptides) may lead to the gradual loss of intramolecular gap areas. This would seriously compromise the matrix ability for intrafibrillar remineralization, which is considered essential in restoring the dentin's mechanical properties. More detailed data of the enzymes responsible and their detailed function in dentin-destructive conditions may not only help to find new and better preventive means, but better preservation of demineralized dentin collagenous matrix may also facilitate true biological remineralization for the better restoration of tooth structural and mechanical integrity and mechanical properties.

440 citations


"Zinc Inhibits Collagenolysis by Cat..." refers background in this paper

  • ...Thereby, remineralization cannot take place in the demineralized zones, eventually leading to tissue loss in dentin structure [Tjäderhane et al., 2015]....

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Journal ArticleDOI
TL;DR: It is concluded that the generation of ICTP and CTX depends on different collagenolytic pathways, which may explain why these two markers may discriminate between different bone pathologies.
Abstract: Bone resorption may generate collagen fragments such as ICTP and CTX, which can be quantified in serum and/or urine by using specific immunoassays, and which are used as clinical markers. However, the relative abundance of ICTP and CTX varies according to the type of bone pathology, suggesting that these two fragments are generated through distinct collagenolytic pathways. In this study, we analyzed the release of ICTP and CTX from bone collagen by the proteinases reported to play a role in the solubilization of bone matrix. Cathepsin K released large amounts of CTX, but did not allow a detectable release of ICTP. Conversely, the matrix metalloproteinases (MMPs) MMP-2, -9, -13, or -14 released ICTP, but did not allow a detectable release of CTX. Next we analyzed the release of ICTP and CTX from bone explants cultured in the presence of well-established inhibitors of these proteinases and of matrix solubilization. An inhibitor of cysteine proteinases including cathepsin K, inhibited the release of CTX, but not the release of ICTP. MMP inhibitors inhibited the release of ICTP, but also that of CTX, in agreement with the putative role of MMPs in the initiation of bone resorption in addition to matrix solubilization. Similarly the treatment of mice bearing bone metastasis with an MMP inhibitor led to a significant reduction of serum ICTP and CTX, and osteolytic lesions. We conclude that the generation of ICTP and CTX depends on different collagenolytic pathways. This finding may explain why these two markers may discriminate between different bone pathologies.

426 citations


"Zinc Inhibits Collagenolysis by Cat..." refers methods in this paper

  • ...…namely CTX (C-terminal cross-linked telopeptide of type I collagen) and ICTP (cross-linked carboxy-terminal telopeptide of type I collagen), into the incubation media was used as an indirect measure of collagen breakdown due to cathepsin K and MMPs, respectively [Garnero et al., 1998, 2003]....

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Trending Questions (2)
Is zinc in collagen peptides?

Cathepsin K-induced dentin collagen degradation can be strongly inhibited by zinc.

Does Collagen peptides have zinc?

Zinc can prevent collagen hydrolysis by MMPs.