Co-distribution of cysteine cathepsins and matrix metalloproteases in human dentin

Abstract

It has been hypothesized that cysteine cathepsins (CTs) along with matrix metalloproteases (MMPs) may work in conjunction in the proteolysis of mature dentin matrix. The aim of this study was to verify simultaneously the distribution and presence of cathepsins B (CT-B) and K (CT-K) in partially demineralized dentin; and further to evaluate the activity of CTs and MMPs in the same tissue. The distribution of CT-B and CT-K in sound human dentin was assessed by immunohistochemistry. A double-immunolabeling technique was used to identify, at once, the occurrence of those enzymes in dentin. Activities of CTs and MMPs in dentin extracts were evaluated spectrofluorometrically. In addition, in situ gelatinolytic activity of dentin was assayed by zymography. The results revealed the distribution of CT-B and CT-K along the dentin organic matrix and also indicated co-occurrence of MMPs and CTs in that tissue. The enzyme kinetics studies showed proteolytic activity in dentin extracts for both classes of proteases. Furthermore, it was observed that, at least for sound human dentin matrices, the activity of MMPs seems to be predominant over the CTs one.

Sodium Trimetaphosphate as a Novel Strategy for Matrix Metalloproteinase Inhibition and Dentin Remineralization

“…Investigations in biology and oral biochemistry have clarified the events that lead to the carious lesion progression and have undermined the traditional concept that cariogenic bacteria enzymes are determinants for the destruction of dentin [Tjäderhane et al, 1998;Caufield and Griffen, 2000;Scaffa et al, 2017]. Different members of the MMP family were localized in sound and caries-affected dentin, both in latent and active forms, including MMPs-2 and -9 [Tjäderhane et al, 1998;Kato et al, 2011], with increased activity in the carious condition .…”

Optimizing resin-dentin bond stability using a bioactive adhesive with concomitant antibacterial properties and anti-proteolytic activities

“…Demineralized collagen matrices of dentin act as scaffolds for resin infiltration during dentin bonding. Nevertheless, the dentin organic matrix contains soluble and matrix-bound endogenous proteolytic enzymes, including MMPs and cysteine cathepsins [52]. These proteolytic enzymes are responsible for degradation of exposed collagen fibrils within the hybrid layers.…”

“…When activated by acid-etchants during dentin bonding, some of the MMPs, specifically MMP-2, MMP-8 and MMP-9, are responsible for degradation of extracellular matrix components [53]. Although dentin type I collagen is highly cross-linked [55], they are still susceptible to the degradation by dentin-specific MMPs [52]. Being the only cysteine cathepsin identified from mineralized dentin, cathepsin K cleaves the telopeptides into slightly shorter fragments than what is achieved by MMPs [56].…”

Inhibition of dentin matrix‐bound cysteine cathepsins by potassium fluoride

“…Endogenous dentin enzymes – including cysteine cathepsins (CCs) K and B, and matrix metalloproteinases (MMPs) 2, 3, 7, 8, 9, and 20 – have the ability to cleave type I collagen fibrils of the dentin organic matrix . These enzymes are normally found in a silent state in mineralized dentin.…”