Art-6

RESTORATİVE DENTİSTRY                                                                                                                                          www.stomaeduj.com




                                                                                                                                                             Review Articles
DENTIN DEGRADOMICS IN DENTIN EROSION
Günçe Ozan1a* , Meriç Berkman2b , Hande Șar Sancaklı1c
1
Department of Restorative Dentistry, Faculty of Dentistry, Istanbul University, TR-34116 Fatih/Istanbul, Turkey
2
Department of Restorative Dentistry, Faculty of Dentistry, Bahçeşehir University, TR-34349 Beşiktaş/İstanbul, Turkey
a
  DDS, PhD, Research Assistant; e-mail: gunce.saygi@istanbul.edu.tr; ORCHID ID: https://orcid.org/0000-0003-1018-3173
b
  DDS, PhD, Assistant Professor; e-mail: mericberkman@gmail.com; ORCHID ID: https://orcid.org/0000-0002-9269-4868
c
 DDS, PhD, Professor; e-mail: handesar@istanbul.edu.tr; ORCHID ID: https://orcid.org/0000-0001-8063-0413

ABSTRACT                                                                              https://doi.org/10.25241/stomaeduj.2022.9(1).art.6

Background Dentin degradomics are the enzymes found in dentin endogenously and are aimed at attacking
organic compounds of the relevant tissue. During dentin demineralization, these enzymes could turn into
the reaction phase and may step up the degradation. Thus, their connection with dentin erosion and tissue
loss should be explained.
Objective The aim of this review was to describe the mechanisms of dentin degradomics, their relation to
dentin erosion, and recent approaches on inhibiting their action.
Data sources A narrative review was performed with a literature search in the PubMed and Google Scholar
electronic databases.
Study selection Reference lists included full papers of any study design, published in peer-reviewed journals
in English till November 2021.
Data extraction Current literature indicates the term of dentin degradomics, and the mechanism of dental
erosion of both enamel and dentin tissues. The inhibition of matrixmetalloproteinase (MMP) enzymes, which
constitute the subgroup of dentin degradomics, was gained from the recent papers listed in the reference
section.
Data synthesis Biocorrosion covers more of the pathological process of the tissue loss however, most
of the dentin degradomics such as MMPs are not covered by the term, biocorrosion. So, the definitions
of biocorrosion and dentin degradomics were discussed in detail. Green tea, chlorhexidine and fluorides
have the ability to inhibit the reaction of MMPs during dentin demineralization with a different state of
mechanisms. Nowadays, other naturally-derived compounds were included in studies such as polyphenols
and flavonoids. Still, more studies are necessary to clarify their mechanism of action and rates of efficiency.
KEYWORDS
Dental Erosion; Dentin Degradomics; Biocorrosion; MMP İnhibitors; Polyphenols.
1. INTRODUCTION                                                                 a surface phenomenon but it showed a mineral
With the transformation of lifestyle dynamics                                   dissolution beneath the surface [2-4]. It was proved
and dietary habits, dental erosion has become an                                that surface wear in the erosion process was
increased concern recently. Erosive tooth wear is an                            heightened with the friction of acidic solution thus,
important oral health problem when considering the                              dental erosion was not only a chemical dissolution but
prolongation of human life and the survival of healthy                          also a pathodynamic surface alteration [5]. Including
dentition with the overall wellness approach. Regarding                         the whole chemical, biochemical, and electrochemical
the ultraconservative dental concept, updated                                   changes within the dental tissues, ‘bio-corrosion’ was
preventive strategies, and the recent technological                             recommended to be used in terms of dental erosion [6].
improvements in the evaluating methods of enamel                                The term bio-corrosion, which is used in the same sense
surface characteristics at both elemental and physical                          as the term “microbiological corrosion” in engineering
levels, dental researchers and clinicians have spent                            branches, has entered the field of dentistry in its
significant efforts to clarify the mechanisms of dental                         broadest sense under its definition. While corrosion
erosion. While only a few articles were available during                        alone describes the chemical, electrochemical,
the 1970s, today there are dozens of researches                                 and physicochemical dissolution of inanimate
either in vivo or in vitro about dental erosion [1].                            substances, the definition of bio-corrosion includes
Dental erosion was previously defined as a sole                                 all the chemical, biochemical, and electrochemical
substance loss by exogenous or endogenous acids                                 changes seen in both hard and soft tissues and body
without bacterial involvement. However, it was                                  fluids in living organisms. These changes are seen
revealed in 2012 that dental erosion was not only                               as either dissolution of the tissue or cell apposition
              OPEN ACCESS This is an Open Access article under the CC BY-NC 4.0 license.
              Peer-Reviewed Article
    Citation: Ozan G, Berkman M, Sar Sancaklı H. Dentin degradomics in dentin erosion. Stoma Edu J. 2022;9(1):55-62.
    Received: December 30, 2021; Revised: January 30, 2022; Accepted: February 15, 2022; Published: February 28, 2022.
    *Corresponding author: Dr. Günçe Ozan, Department of Restorative Dentistry, Faculty of Dentistry, Istanbul University, TR-34116 Fatih/Istanbul, Turkey
    Tel.: +902124142020; Fax: +902125312230; e-mail: gunce.saygi@istanbul.edu.tr
    Copyright: © 2022 the Editorial Council for the Stomatology Edu Journal.




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                    by inducing tissue growth. Ulcers, vascular ruptures,      through deeper layers of both enamel and dentin
Review Articles     or muscle injuries in living organisms as a result of      tissues [1]. With the non-ionized acidic exposure, the
                    tissue dissolution or induction of tissue growth, even     inorganic part of dentin dissolves and collagens of the
                    cancer cases may develop [7]. In the field of dentistry,   organic structure are revealed. Thus, the pathodynamic
                    pathologic stages of bio-corrosion reveal mostly on        process of the erosion continues with the surface
                    the development of dental caries and erosion. In           alterations leading to wear and substance losses.
                    the following parts of the current review, the term        Although it was reported that “bio-corrosion”, which
                    “bio-corrosion”, its relation to dentin degradomics,       reveals all pathological changes comprehensively,
                    and recent updates on inhibiting endogenous                has not yet replaced the term “dental erosion” but
                    etiologies of dentin erosion are clarified in detail.      is thought to become widespread in the fields of
                                                                               dentistry [6].
                    2. METHODOLOGY                                              Table 1. Processes in bio-corrosion.
                                                                                Processes in Bio-corrosion
                    The article search for this literature review utilized
                                                                                1) Endogenous Dental plaque (biofilm) &
                    PubMed and Google Scholar, and the selection
                                                                                acid intake   Gingival crevicular fluid
                    included articles published in peer-reviewed journals
                    in English. The terms used for the introduction part                                    Gastric hydrochloric acid
                    were “Dentin Erosion” and “Dentin Degradomics”. Due         2) Exogenous acid Diet /Nutrition style
                    to explaining the terms in detail and to the terms          intake            Profession/Occupation
                    being highly up-to-date, no time limit was applied and
                    published articles were looked through till November        3) Proteolysis              Enzymatic lysis (In dental caries
                    2021. To reach a clinical point of action, a branch of                                  formation)
                    dentin degradomics, matrix metalloproteinase (MMP)                                      Proteases (Pepsin and Trypsin)
                    enzymes, which have been appearing in many studies
                                                                                4) Electrochemical Piezoelectric effect on dentin
                    for a while, and recent chemical compounds used
                                                                                effect
                    to inhibit MMPs were also considered. The search
                    excluded: monographs and case reports.                     Just as the histology of erosion differs from caries, the
                                                                               morphology of dentin is mainly varied from enamel.
                    3. RESULTS                                                 Thus, the responses of the two tissues with different
                                                                               contents against acid attacks are highly distinctive.
                    Dental caries is a pathology caused by bacterial           Compared to enamel, the mineral content of dentin
                    acids that have settled and grown in the biofilm of        diminished, and its organic content is higher. The major
                    the dental–mostly enamel- hard surfaces. Dental            component of its organic matrix is Type 1 collagen and
                    caries begin with the dissolution of hydroxyapatites       other components that are contributed to trace are
                    of enamel, and a small amount of destruction               non-collagenous phosphoprotein, glycoprotein, lipid,
                    (proteolysis) occurs in the proteins in the enamel.        and proteoglycan. While the amount of carbonate is
                    Simply, the pathology of dental caries is again a          approximately 3% in the enamel, this value is 5-6%
                    bio-corrosion process, as it includes a biochemical        in dentin, therefore dentin dissolves more easily with
                    beginning (acid production of bacteria) and protein        acids. On the other hand, the crystals in dentin are
                    degradation (proteolysis).                                 smaller than those in enamel; thus, the surface area of
                    The term “erosion” does not include material losses        dentin exposed to acid attacks is relatively higher [8].
                    caused by biochemical and electrochemical processes        Erosion in enamel tissue, which has 95% inorganic
                    on dental hard surfaces. The biochemical changes           structure, starts with a softening on the surface by the
                    induced by “proteolysis” and the electrochemical           dissolution of the structure and results in permanent
                    reactions that occur as a result of the piezoelectric      loss of demineralized tissue with ongoing acid attacks
                    effect on the surface are better defined by the term       (Fig. 1) [9]. However, erosion comprises two separate
                    “bio-corrosion”. To sum up, bio-corrosion is caused by     events in dentin, the dissolution of the existing
                    acids coming from both internal and external sources,      inorganic structure and the realization of proteolytic
                    proteolytic enzymes (pepsin and trypsin), piezoelectric    destruction with the endogenous enzymes (Fig. 2).
                    effects - in the dentin because of releasing Ca+2 ions
                    from the tooth surface during dentinal wear- [5], and
                    factors that cause dissolution in the inorganic and
                    organic matrix of dentin after enamel degradation.
                    Enzymes such as matrix metalloproteinases, which are
                    endogenously found in the structure, are not included       Figure 1. Dental erosion limited to enamel tissue of teeth #21 and slight
                    in the bio-corrosion mechanism. The biochemical            changes in the surface of teeth #11.
                    events covered by bio-corrosion are shown in Table 1.      The beginning of dentin erosion, inorganic struc-ture,
                    This pathodynamic process begins subsurface by             because of their structural differences, acts distinctively
                    dissolving minerals likewise caries lesions. In the        as well. At first, peritubular and intertubular dentin
                    sequel, ionized H+ ions are released from the enamel       begin to dissolve at the same rate. However, after
                    tissue by acid attacks and non-ionized H+ ions pass        the first minute, the intertubular dentin area remains



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                                                                                                                                         Review Articles
more stable, but the peritubular dentin continues to                       demineralization by also considering the histological
dissolve rapidly, and the dentinal tubules expand.                         structure of dentin [15,16]. Ganss et al. (2014) reported
                                                                           that when the organic matrix is chemically removed
                                                                           by either enzymes or mechanical forces (abrasion)
                                                                           [16], the erosive agent directly encounters the
                                                                           mineralized tissue, which dissolves quickly. However,
                                                                           in the presence of an organic matrix, the pH decrease
                                                                           in the environment slows down, and accordingly, the
                                                                           erosion rate reduces as well. Thus, the organic matrix
                                                                           has the feature of limiting the mineral outflow (ionic
                                                                           diffusion) towards the external environment from the
                                                                           tooth surface [17]. For these reasons, it is clear that the
                                                                           organic matrix has a protective role in erosive wear.
                                                                           DOM is resistant to brushing forces up to 4 Newtons
                                                                           (N) so that it can protect the remaining dentin surface
 Figure 2. Dental erosion passed through dentin and loss of structure.     against mechanical trauma such as toothbrush
As the acid attack continues, the mineral loss                             abrasion [18]. However, although this layer is
is significantly reduced due to the decreasing                             resistant to physical factors, it can be dissolved by
demineralization rate and the demineralized area                           enzymatic reactions [16]. Considering that erosive
reaches a certain thickness [10]. The degree of mineral                    demineralization does not occur in the presence of
loss is supplied by the buffering feature of collagens                     bacteria, it is certain that host-derived enzymes are
so that further loss of substance is prevented by                          responsible for the destruction of DOM, which has
the dissolved minerals, which brings the ionic level                       been proven by clinical studies [14,19].
of the environment to the approximate saturation                           Recently, a new category of enzymes has been found
level. While acid attacks continue to a clinically                         and named “Dentin Degradomics” which were aimed
significant concentration and time, the inorganic part                     to degrade the organic matrix, the collagen layer,
dissolves easily as well. Depending on the potential                       endogenously [20]. It was shown in the studies that
and duration of action of the erosive agent, at first, a                   degradomics consist of collagenolytic enzymes and
completely demineralized layer and then a partially                        MMPs which are stable in the organic matrix from
demineralized layer of dentin appears, followed by a                       the formation of dentin tissue. These enzymes are
completely sound dentin layer. However, the partially                      mainly responsible for the catabolic reactions of
demineralized area in the middle is not present in                         the organic matrix and their mechanism of action
every case [1].                                                            depends on the pH of the environment [21,22].
Although the inorganic content dissolves away with                         When the pH decreases at erosive demineralization,
the erosive attack, the organic matrix remains intact                      these enzymes become activated and when it turns
and forms a barrier against acid attacks, preventing                       neutral, they start to degrade the collagens of the
further mineral release from the dental tissue and                         organic matrix and contribute to the improvement of
stopping the progression of the erosive lesion as                          erosive demineralization [23]. These MMPs are found
mentioned above [11-13]. However, it is thought                            in various tissues of the body and they have been
that some of the proteolytic enzymes in the dentin                         secreted when tissue remodeling is needed without
structure are activated by acidic pH and these enzymes                     any pathological circumstances. MMPs are divided
increase the rate of erosion by causing the dissolution                    into 6 groups according to their structural properties
of the demineralized organic matrix (DOM). For                             and substrate specificity: Collagenases, Type IV
this reason, a new field has emerged to investigate                        collagenases (gelatinases), stromelysins, matrilysins,
the functions and mechanisms of these enzymes                              membrane-type MMPs (MT-MMP) and others such as
called “Dentin Degradomics” [14]. Subsequently,                            enamelysine (MMP-20) [24]. Not all of these enzymes
many studies have been developed to clarify the                            are found in dentin but the ones which are presented
role of the organic matrix in the stages of erosive                        in the dentin are shown in Table 2.
 Table 2. Classification of various degradomic enzymes (Endogenous collagenolytic dentinal enzymes).* [14,24]
 Group              Enzyme             Nomenclature Function
              Neutrophile                                    It is found frequently at dentinal levels and related highly to carious
 Collagenases                          MMP-8
              collagenase                                    activity in dentin.
                    Gelatinase A       MMP-2                 Telopeptidase activity to Type I collagen in organic matrix.
 Gelatinases
                    Gelatinase B       MMP-9                 Odontoblasts may express these gelatinases.
                                                             It has the proteoglycanase activity which may affect the activity of
 Stromelysins Stromelysin 1 MMP-3
                                                             some of the cathepsins.
                                                             It has shown to process dentinsialophosphoprotein* and found in
 Other MMPs         Enamelisin         MMP-20
                                                             dentinal tubules of caries-affected dentin.
 Cysteine                              Cathepsin B
                    Cathepsin                                They show the gelatinolytic activity.
 cathepsins                            Cathepsin K
 *Not related to carious or erosive demineralization.




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                    Another family of collagenolytic enzymes, cysteine                   may be better in order to understand their role in the
Review Articles     cathepsins (CC), are activated at neutral pH, unlike                 progression of erosive lesions.
                    MMPs. However, they need slightly acidic pH to
                    function [25]. Because of these properties, it is known              4. DISCUSSION
                    that MMPs start to function at the point where CCs
                    lose their functions. Since acidic pH is only durable for            The protection of DOM by MMP inhibitors is the
                    a while in dentin erosion, MMPs are thought to play a                recent approach to the prevention of dentin erosion
                    superior role in collagen degradation than cathepsins                [26]. Among the different types of MMP inhibitors,
                    [26]. Cysteine cathepsins found in the dentin are also               chlorhexidine (CHX), and epigallocatechin gallate
                    shown in Table 3.                                                    (EGCG) as a polyphenolic compound, have been
                     Table 3. Matrixmetalloproteinase (MMP) inhibitors.                  the most common compounds evaluated as part
                          MMP                                                            of preventive strategies to reduce erosive dentin
                                                Type                      Function       demineralization. Indeed, their mechanism of action is
                        inhibitor
                                                           Found to have
                                                                                         yet to be estimated. MMP inhibitors that have recently
                                                           inhibitory properties         been reported in studies are summarized in Table 3.
                                         Epigallocatechin-                               Polyphenols are used frequently in many research
                     Polyphenols                           against MMP-2 and-
                                         3-gallate (EGCG)                                projects and specifically polyphenols isolated from
                                                           9 and the activation
                                                           of MMP-8 [1,26,27].           green tea, especially epigallocatechin-3-gallate
                                                                Reported to inhibit      (EGCG) that was found to have inhibitory properties
                                         Theaflavin                                      against MMP-2 and -9 [27] and the activation of MMP-
                                                                MMP-2 and -9 [50].
                                                                                         8, which acts for the remineralization in demineralized
                                                                Showed
                                                                                         dentin [1,28]. According to the information obtained,
                                                                collagenolytic
                     Phenolic acid       Anacardic acid                                  these catechins accumulate on the organic material
                                                                activity against
                                                                MMP-2 [52].              in dentin [29] and run by masking the catalytic site of
                                                                                         MMP-2 or cause structural changes with its hydrogen
                     Natural                                    Reported to inhibit
                                         Quercetin                                       bonds and hydrophobic linkages to collagenase [28].
                     flavonoids                                 MMP-2 and -9 [54].
                                                                                         The effect of EGCG against degradomics was proven
                                                                Has the ability to       in previous studies [23,29,30,31] and its effectiveness
                     Non-flavonoid
                                   Resveratrol                  reduce MMP-9             was compared usually to various formulae of
                     polyphenol
                                                                expression [56].
                                                                                         fluorides or CHX. These compounds have also shown
                                                                Has the ability to       efficiency against MMPs but with distinctive targeting
                                                                inhibit MMP-2 and -9     procedures. To better explain, MMP enzymes are
                                                                at the concentration     zinc-activated and calcium-dependent enzymes.
                     Chlorhexidine
                                         Bisbiguanide           of 0.03% completely,
                     (CHX)                                                               By chelating these cations, chlorhexidine binds to
                                                                and MMP-8 at the
                                                                                         the sulfhydryl groups and/or cysteines in the active
                                                                concentration of
                                                                0.01-0.02% [27].         parts of MMPs and inhibits the enzyme activity [32].
                                                                                         However, the inhibitory activity of chlorhexidine is
                                         Some of
                                                                Inhibit the activation   directly related to its concentration. CHX can cause
                                         the fluoride
                     Fluorides                                  of MMPs by ion-          protein denaturation at saliva concentrations above
                                         compounds (eg.
                                                                blocking [32].           0.2%, reduce the solubility of dentin collagen and
                                         NaF)*
                                                                                         prevent the progression of dentin erosion. Besides,
                     * Not all of the fluoride compounds are enlightened to contribute
                                                                                         chlorhexidine could completely inhibit MMP-2 and
                     MMP inhibition.
                                                                                         -9 at the concentration of 0.03%, and MMP-8 at
                    In the acidic environment, dentin demineralization                   the concentration of 0.01-0.02% [28]. Furthermore,
                    occurs, collagen fibrils are exposed, and the MMPs                   it was reported that fluorides, thanks to their high
                    in dentin and saliva are activated simultaneously.                   electronegativity, prevent Zn2+ and Ca2+ ions, which
                    However, when the pH rises to neutral, MMPs degrade                  are necessary for the activation of MMPs, from entering
                    the triple helix structure of collagens, start to dissolve           the catalytic activities as similar as the inhibitory
                    organic matrix and increase the rate of dentin loss [26].            activity of CHX [33].
                    In addition, these enzymes cause structural changes                  The effect of different types of ion-containing fluoride
                    in existing collagens. The parts called “telopeptides” at            compounds (such as stannous fluoride, titanium
                    the ends of the collagens are dissolved and removed,                 tetrafluoride, amine fluoride) on dental erosion is
                    thus, spaces are created in the internal structure of the            attributed to the protective layer formed on the dentin
                    molecule. The relevant structural dissolution prevents               surface, it is not yet clear whether or not they perform
                    interfibrillar remineralization, which is crucial for                MMP inhibition. Since sodium (Na+) ion does not form
                    strengthening the mechanical properties of dentin.                   a layer similar to other ionic fluoride components
                    It also causes the loss of non-collagen matrix proteins,             on dentin surface, the most widely used fluoride
                    which act as nuclei for remineralization. Still, the exact           compound in studies is NaF. In a study, it was found
                    contribution of these highly collagenolytic enzymes to               that by using the gelatin zymography ,may inhibit the
                    the progression of erosion is not known so far. Using                activity of MMP-2 and -9 in a dose-dependent manner
                    specific inhibitors for these distinct classes of enzymes            [34]. 200 ppm fluoride can inhibit pro and active forms



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of MMP-2 and active forms of MMP-9 by 100%. If these       the collagenolytic activity of anacardic acids against




                                                                                                                       Review Articles
rates are constant at 225 ppm, the pro-form of MMP-        MMP-2 had also been proven by zymographic analysis
9 could be inhibited approximately by 85%; pro and         and in vitro evaluation revealed reduced dentinal wear
active forms of salivary MMP-9 were inhibited by 55%.      compared to EGCG and NaF [51,52].
While the inhibitory activity of NaF against MMP-2         On the other hand, another approach to inhibit
and -9 is reversible at low concentrations, it has been    erosive wear has exhibited promising results which
reported that it is irreversible at high concentrations    aimed to enhance protecting properties of acquired
such as 5000 ppm [34].                                     pellicle. The adsorbtion of polyphenolic compounds
There have been studies comparing the effect of            (EGCG, epicatechin-3-gallate (ECG), and theaflavin)
fluorides (especially sodium fluoride, NaF), on EGCG,      onto the pellicle may lead to stabilize the structure
and CHX [35,36]. Regarding the variances differed          [38] and increase its thickness [53] resulting in an
highly in the methodological section of the studies,       anti-erosive effect. So that, dental materials such
most of them could not be compared directly with           as gels or varnishes including polyphenols were
one-to-another. One of the differences encountered         demonstrated in studies [33,38] which were tested
in the studies is the frequent application of the          against both enamel and dentin erosion. However,
contact profilometer to measure dentin loss [30,36,37].    due to the structural variations of enamel and
However, some controversies have arisen regarding its      dentin, such as the higher porosity of dentin, the
usage at erosive dentin surfaces because of the tip of     preventive effect of the acquired pellicle could be
the profilometer that could cause damage by pressing       reduced. Methodologies involving gels usually engage
the DOM [38]. Thus, to overcome this problem, some         polyphenolic compounds as active compounds and
studies have used non-contact [39,40] or digital           compare their effect against a fluoride gel [30,38].
microscopy [41]. As another solution, to minimize          However no commercial products have figured yet,
the shrinkage of DOM, some analysis of the contact         except the mouthwashes with green tea aromas. For
profilometer had been done at 100% humidity [38].          instance, gels containing EGCG and CHX showed to
Another variation among studies with respect to the        increase a protein (Statherin) in the acquired pellicle,
method is that the erosive cycles. Most of the cycles      which increased the saturation of oral fluids by
were done with Cola [35,42,43] but some studies            releasing Ca+2 and PO-4 ions following acid attacks [38].
have used various acidic solutions, such as citric acid    Another study reported that resin materials containing
[40,44] or hydrochloric acid [45,46]. Moreover, many       EGCG increased basic isoforms of salivary proteins
of the studies have used not only the erosive cycle        which may perform to improve the acid resistance of
but also ‘erosive+abrasive’ cycles [38,45] so, within      demineralized surfaces [54].
the changes in the methodology, the scores of dentin       More recently, flavonoids, which are from the
losses highly vary. Besides, the concentrations of the     subgroups of polyphenolic compounds, have
active ingredients or the ratios of the extractions have   been frequently investigated in studies comprising
varied following the type of formula, such as gels [30],   MMP inhibition [44,55]. Quercetin is one of the
toothpaste [37], and mouthwashes [28,35], as well.         natural flavonoids which is found highly in fruits
Still, the main outcome of these studies is that MMP       and vegetables and has been reported to have the
inhibitors play an active role in reducing dentin loss     potential to protect against degradation of the
by protecting DOM.                                         collagen matrix by inhibiting MMP-2 and MMP-9
Within the differences among studies evaluating            [56]. An in vitro study showed that quercetin showed
EGCG, CHX, and NaF, one point is described that            significantly lower microhardness loss than CHX,
EGCG had slightly more action against dentin erosion       EGCG, and NaF groups and revealed a thicker DOM
in another different way. Previous studies [30,47]         than control dentin [44]. This dose-dependant
suggest that the protease inhibitors have the ability      outcome of quercetin was explained by its improving
to minimize the degradation of DOM against dentin          effect on collagen resistance as a result of inhibiting
demineralization. Besides, polyphenols are reported        both free- and collagen-bound degradomics (MMPs)
to improve the mechanical properties of the organic        in dentin [57]. On the other hand, previous studies
matrix and resist enzymatic degradation [42]. So           have shown that resveratrol significantly reduces
recently, plant polyphenols have been investigated         MMP-9 expression [58], which is a non-flavonoid
against dentin erosion so that potential benefits          polyphenol found in many of the plants. Since there
could be gained. One of them is ‘theaflavin’, which is     is no study that has investigated its protective effect
the most frequent polyphenol in black tea, formed          against MMPs, there are studies reporting its benefit
by the oxidation of catechins during manufacturing         on dentin bonding durability [55,59] and as anticaries
[48]. Aside from the antifungal [48], antioxidant, and     agent [60].
antimutagenic effects of theaflavins, they were also
reported to inhibit MMP-2 and MMP-9 [49,50]. In an in      5. CONCLUSION
vitro study, the aflavins showed similar dentin losses
to EGCG and commercial green tea with no significant       Since dental erosion is a complex situation, there are
difference [46]. Anacardic acid is also one of the         debates on terming it as “bio-corrosion” in order to
phenolic acids obtained from the shell of the cashew       explain the process more comprehensively. Besides,
nut. Accompanied by the antioxidant capacity [50],         endogenous enzymes called degradomics have


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                    Ozan G, et al.
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                    also detrimental effects on the process if they reach                        AKNOWLEDGEMENTS
Review Article      exposed dentin surfaces. There have been inhibitory                          None.
                    materials such as fluorides, chlorhexidine, and green
                    tea extracts that were proved to protect demineralized                       CONFLICT OF INTEREST
                    collagen matrix. Studies are being carried out on
                                                                                                 The authors have certified that there is no conflict of interest.
                    the novel polyphenolic compounds that could be
                    beneficial to collagenolytic processes. Their effect
                    should be further investigated and comparably                                AUTHOR CONTRIBUTIONS
                    evaluated with recently known MMP inhibitors in                              GO: conceptualization, resources, writing-original draft preparation,
                    various concentrations. So that, research may solve                          visualization, project administration. GO,MB: methodology,
                    the inhibition mechanism and clinicians may benefit                          software, investigation, data curation. GO,MB,HSS: formal analysis,
                    from the enhancement of their process.                                       writing-review and editing. MB,HSS: validation. HSS: supervision.

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    60              Stoma Edu J. 2022;9(1): 55-62                                                                    pISSN 2360-2406; eISSN 2502-0285
Dentin degradomics
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Stoma Edu J. 2022;9(1):55-62                                                                pISSN 2360-2406; eISSN 2502-0285                         61
                     Ozan G, et al.
www.stomaeduj.com



                                                                                                            Günçe OZAN
Review Articles
                                                                                               DDS, PhD, Research Assistant
                                                                                         Department of Restorative Dentistry
                                                                                                        Faculty of Dentistry
                                                                                                         Istanbul University
                                                                                             TR-34116 Fatih/Istanbul, Turkey
                    CV
                    Günçe Ozan received her DDS in 2011 from the Faculty of Dentistry at Istanbul University, Istanbul, Turkey. She immediately
                    started her PhD at the Restorative Dentistry Department of the same university. After studying on the fields of dental erosion
                    and preventive dentistry, she had her PhD degree in 2017. She worked at the Young Dentists' Commission of the Turkish Dental
                    Association for 2 years. She is now continuing her career at the Istanbul University as a Research Assistant.



                    Questions
                    1. The difference between the terms, “Dental erosion” and “Bio-corrosion” distinguishes
                    from the certain reactions that were occurred during dental erosion?
                    q a. Piezoelectric effect;
                    q b. Proteolysis;
                    q c. Piezoelectric effect & Proteolysis;
                    q d. Electrochemical effect.
                    2. Demineralization occurs... in dental erosion.
                    q a. Subsurface;
                    q b. Surface and subsurface;
                    q c. Surface;
                    q d. Beneath the surface.
                    3. Which of the enzyme groups of degradomics are not localized in the “dentin”?
                    q a. Enamelisin;
                    q b. MT-MMP;
                    q c. MMP-2;
                    q d. MMP-3.
                    4. MMP enzymes activated at … ph but, functioned at… ph.
                    q a. Acidic / basic;
                    q b. Basic / neutral;
                    q c. Neutral / acidic;
                    q d. Acidic / neutral.




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    62              Stoma Edu J. 2022;9(1): 55-62                                                    pISSN 2360-2406; eISSN 2502-0285