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

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 m<smlcap>M</smlcap>. 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 m<smlcap>M</smlcap> (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 m<smlcap>M</smlcap> can be considered as a reliable threshold for the stabilization of dentin matrices.

Enhancing the Stability of the Resin–Dentin Bonding Interface with Ag+- and Zn2+-Exchanged Zeolite A

“…Dental materials containing Ag + zeolites showed better antibacterial activity than those containing CHX . Besides the antibacterial activity, Zn 2+ can also inhibit the activity of endogenous enzymes, protect the collagen fibers from degradation, and promote the remineralization process. , CHX can competitively and reversibly bind to the catalytic active sites of endogenous enzymes and inhibit collagen degradation by endogenous enzymes. , However, Zn 2+ can competitively bind to the cleavage sites of endogenous enzymes on the collagen structure, thus preventing or retarding the degradation of collagen by endogenous enzymes. , CHX can exert the endogenous enzyme inhibition for 24 h, while Zn 2+ can prevent collagen degradation for 4 weeks. In a word, Zn 2+ is a more potent, stable, and effective inhibitor for endogenous enzyme-mediated collagen degradation than CHX. , Therefore, the inorganic sources of Ag + and Zn 2+ with slow-release characteristics might be useful in enhancing the stability of the resin–dentin bonding interface.…”

“…17 Besides the antibacterial activity, Zn 2+ can also inhibit the activity of endogenous enzymes, protect the collagen fibers from degradation, and promote the remineralization process. 18,19 CHX can competitively and reversibly bind to the catalytic active sites of endogenous enzymes and inhibit collagen degradation by endogenous enzymes. 20,21 However, Zn 2+ can competitively bind to the cleavage sites of endogenous enzymes on the collagen structure, thus preventing or retarding the degradation of collagen by endogenous enzymes.…”

Zinc–Calcium–Fluoride Bioglass-Based Innovative Multifunctional Dental Adhesive with Thick Adhesive Resin Film Thickness

“…Subsequent research has also promoted the use of collagen cross-linkers that, besides antienzymatic effects, make the exposed collagen more resistant against degradation . Although zinc at physiological concentrations is a necessary element for collagen hydrolysis by MMPs, it was also reported to act as a potential MMP inhibitor at high concentrations . Especially, MMP-2 and MMP-9 are inhibited by zinc and other metals. , Loading an adhesive with zinc that can gradually be released to the immediate dentin environment may help to retard biodegradation of adhesive interfaces.…”

The inhibitory effect of carboxyl-terminated polyamidoamine dendrimers on dentine host-derived matrix metalloproteinases in vitro in an etch-and-rinse adhesive system

“…The use of synthetic and natural cross-linkers has been confirmed to increase the mechanical performance of dentine [6][7][8] by facilitating additional collagen cross-linking [9][10][11] and inactivating endogenous dentine MMPs [12,13] mainly by concealing the cleavage sites of collagen [14] and/or altering the spatial structure of proteases, resulting in enhanced resistance against the enzymic degradation of dentine matrix. MMPs inhibitors, such as chlorhexidine, quaternary ammonium salts and zinc, are applied to suppress collagenolytic activity in the dentine-collagen matrix due to changes in protein configuration or to disturb the protease-activating process [5,[15][16][17]. Similar to collagen cross-linkers, the main drawback of non-specific inhibitors to inactivate MMPs and cysteine cathepsins is the residue of the water-rich, resin-sparse and mineral-depleted collagen matrix within the HL.…”