scholarly journals Matrix Metalloproteinases and Other Matrix Proteinases in Relation to Cariology: The Era of ‘Dentin Degradomics'

2015 ◽  
Vol 49 (3) ◽  
pp. 193-208 ◽  
Author(s):  
Leo Tjäderhane ◽  
Marília Afonso Rabelo Buzalaf ◽  
Marcela Carrilho ◽  
Catherine Chaussain
Keyword(s):  
Mechanical Properties ◽  
Matrix Metalloproteinases ◽  
Type I Collagen ◽  
Resin Composite ◽  
Hydrolytic Degradation ◽  
Organic Matrix ◽  
Type I ◽  
Restorative Treatment ◽  
Cysteine Cathepsins ◽  
Demineralized Dentin

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.

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

2017 ◽  
Vol 51 (6) ◽  
pp. 576-581 ◽  
Author(s):  
Pinar Altinci ◽  
Roda Seseogullari-Dirihan ◽  
Gulsen Can ◽  
David Pashley ◽  
Arzu Tezvergil-Mutluay
Keyword(s):  
Matrix Metalloproteinases ◽  
Mass Loss ◽  
Type I Collagen ◽  
Cathepsin K ◽  
Collagen Degradation ◽  
Type I ◽  
Level Control ◽  
Physiological Level ◽  
Cysteine Cathepsins ◽  
Demineralized Dentin

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.

scholarly journals Biomineralization and Biomaterial Considerations in Dentin Remineralization

2016 ◽  
Vol 1 (1) ◽  
pp. 7-12 ◽  
Author(s):  
Xu Zhang ◽  
Zuohui Xiao ◽  
Haorong Wang ◽  
Anil Kishen
Keyword(s):  
Minimally Invasive ◽  
Type I Collagen ◽  
Organic Matrix ◽  
Type I ◽  
Hard Tissue ◽  
The Past ◽  
Organic Matrices ◽  
Caries Management ◽  
Inorganic Matrix ◽  
Demineralized Dentin

ABSTRACT Dentin is a composite hard tissue, comprising of inorganic and organic matrices, and regulated by many proteins during development. The demineralization of dentin results from the loss of inorganic matrix [mainly hydroxyapatite (HAP)], but the organic matrix (mainly type I collagen) will sustain for a period of time after demineralization. Over the past decade, there has been a growing interest on the remineralization of demineralized dentin, primarily in connection with minimally invasive caries management. More and more biomaterials and methods are currently being evaluated to achieve newer approaches for the remineralization of demineralized dentin. These strategies are mostly based on biomimetic approaches and aim to achieve the characteristics of natural hard tissue. This article will present a complete review on the basic compositions and properties of dentin, which formed the basis for the biomimetic remineralization of demineralized dentin. How to cite this article Zhang X, Xiao Z, Wang H, Kishen A. Biomineralization and Biomaterial Considerations in Dentin Remineralization. J Oper Dent Endod 2016;1(1):7-12.

Role of Host-Derived Proteinases in Dentine Caries and Erosion

2015 ◽  
Vol 49 (Suppl. 1) ◽  
pp. 30-37 ◽  
Author(s):  
Marília Afonso Rabelo Buzalaf ◽  
Senda Charone ◽  
Leo Tjäderhane
Keyword(s):  
Structural Changes ◽  
Type I Collagen ◽  
Organic Matrix ◽  
Collagen Matrix ◽  
Type I ◽  
Cysteine Cathepsins ◽  
Gradual Loss ◽  
Collagen Molecules ◽  
And Function

Demineralization in dentinal caries and erosion exposes dentine organic matrix. This exposed matrix, containing type I collagen and non-collagenous proteins, is then degraded by host collagenolytic enzymes, matrix metalloproteinases (MMPs) and cysteine cathepsins. The knowledge of the identities and function of these enzymes in dentine has accumulated only within the last 15 years, but has already formed a field of research called ‘dentine degradomics'. This research has demonstrated the role of endogenous collagenolytic enzymes in caries and erosion development. In demineralized dentine, the enzymes degrade triple-helical collagen molecules, leading to the gradual loss of collagen matrix. Even before that, they can cleave off the terminal non-helical ends of collagen molecules called telopeptides, leading to the structural changes at the intramolecular gap areas, which may affect or even prevent intrafibrillar remineralization, which is considered essential in restoring the dentine's mechanical properties. They may also cause the loss of non-collagenous proteins that could serve as nucleation sites for remineralization. Here we review the findings demonstrating that inhibition of salivary or dentine endogenous MMPs and cysteine cathepsins may provide preventive means against the progression of caries or erosion. Furthermore, we also suggest the future directions for the new experimental preventive research to gain more knowledge of the enzymes and their function during and after dentine demineralization, and the pathways to find the clinically acceptable means to prevent the functional activity of these enzymes.

Collagen-the Ultrastructural Element of the Bone Matrix

2018 ◽  
Vol 69 (7) ◽  
pp. 1706-1709
Author(s):  
Nicoleta Dumitru ◽  
Andra Cocolos ◽  
Andra Caragheorgheopol ◽  
Constantin Dumitrache ◽  
Ovidiu Gabriel Bratu ◽  
...  
Keyword(s):  
Type I Collagen ◽  
Bone Microarchitecture ◽  
Complex Structure ◽  
Bone Matrix ◽  
Organic Matrix ◽  
Bone Diseases ◽  
Bone Collagen ◽  
Type I ◽  
New Therapeutic Approaches ◽  
And Function

There is an increased interest and more studies highlight the fact that bone strength depends not only on bone tissue quantity, but also on its quality, which is characterized by the geometry and shape of bones, trabecular bone microarchitecture, mineral content, organic matrix and bone turnover. Fibrillar type I collagen is the major organic component of bone matrix, providing form and a stable template for mineralization. The biomedical importance of collagen as a biomaterial for medical and cosmetic purposes and the improvement of the molecular, cellular biology and analytical technologies, led to increasing interest in establishing the structure of this protein and in setting of the relationships between sequence, structure, and function. Bone collagen crosslinking chemistry and its molecular packing structure are considered to be distinct features. This unique post-translational modifications provide to the fibrillar collagen matrices properties such as tensile strength and viscoelasticity. Understanding the complex structure of bone type I collagen as well as the dynamic nature of bone tissues will help to manage new therapeutic approaches to bone diseases.

Intrinsic mechanical properties of the extracellular matrix affect the behavior of pre-osteoblastic MC3T3-E1 cells

2006 ◽  
Vol 290 (6) ◽  
pp. C1640-C1650 ◽  
Author(s):  
Chirag B. Khatiwala ◽  
Shelly R. Peyton ◽  
Andrew J. Putnam
Keyword(s):  
Mechanical Properties ◽  
Type I Collagen ◽  
Focal Adhesions ◽  
Microscopic Analysis ◽  
Maximal Activity ◽  
Type I ◽  
Cell Functions ◽  
Collagen Density ◽  
Cells Cultured ◽  
In Cells

Mechanical cues present in the ECM have been hypothesized to provide instructive signals that dictate cell behavior. We probed this hypothesis in osteoblastic cells by culturing MC3T3-E1 cells on the surface of type I collagen-modified hydrogels with tunable mechanical properties and assessed their proliferation, migration, and differentiation. On gels functionalized with a low type I collagen density, MC3T3-E1 cells cultured on polystyrene proliferated twice as fast as those cultured on the softest substrate. Quantitative time-lapse video microscopic analysis revealed random motility speeds were significantly retarded on the softest substrate (0.25 ± 0.01 μm/min), in contrast to maximum speeds on polystyrene substrates (0.42 ± 0.04 μm/min). On gels functionalized with a high type I collagen density, migration speed exhibited a biphasic dependence on ECM compliance, with maximum speeds (0.34 ± 0.02 μm/min) observed on gels of intermediate stiffness, whereas minimum speeds (0.24 ± 0.03 μm/min) occurred on both the softest and most rigid (i.e., polystyrene) substrates. Immature focal contacts and a poorly organized actin cytoskeleton were observed in cells cultured on the softest substrates, whereas those on more rigid substrates assembled mature focal adhesions and robust actin stress fibers. In parallel, focal adhesion kinase (FAK) activity (assessed by detecting pY397-FAK) was influenced by compliance, with maximal activity occurring in cells cultured on polystyrene. Finally, mineral deposition by the MC3T3-E1 cells was also affected by ECM compliance, leading to the conclusion that altering ECM mechanical properties may influence a variety of MC3T3-E1 cell functions, and perhaps ultimately, their differentiated phenotype.

Assembly of type I collagen: fusion of fibril subunits and the influence of fibril diameter on mechanical properties

2000 ◽  
Vol 19 (5) ◽  
pp. 409-420 ◽  
Author(s):  
David L. Christiansen ◽  
Eric K. Huang ◽  
Frederick H. Silver
Keyword(s):  
Mechanical Properties ◽  
Type I Collagen ◽  
Type I ◽  
Fibril Diameter

Pharmacological inhibitors to identify roles of cathepsin K in cell-based studies: a comparison of available tools

2009 ◽  
Vol 390 (9) ◽  
Author(s):  
Sylvie Desmarais ◽  
Frédéric Massé ◽  
M. David Percival
Keyword(s):  
Human Cell ◽  
Type I Collagen ◽  
Cathepsin K ◽  
The Other ◽  
Enzyme Assays ◽  
Type I ◽  
Treatment Of Osteoporosis ◽  
Cysteine Cathepsins ◽  
Rodent Cell ◽  
Enzyme Selectivity

Abstract Cathepsin K (Cat K) degrades bone type I collagen and is a target for the pharmacological treatment of osteoporosis. Further roles for Cat K have been recently described, some of which are supported by the use of purportedly selective Cat K inhibitors in human and rodent cell-based assays. Twelve commercial and non-commercial Cat K inhibitors were profiled against a panel of purified human, rat, and mouse cysteine cathepsins and in two cell-based enzyme occupancy assays for activity against Cat K, B, and L. Ten inhibitors, including the carbohydrazide Cat K inhibitor II (Boc-Phe-Leu-NHNH-CO-NHNH-Leu-Z), the non-covalent K4b, and the epoxide NC-2300, have either little Cat K selectivity, or appear poorly cell penetrant. The amino-acetonitrile-containing inhibitors L-873724 and odanacatib show greater than 100-fold human Cat K enzyme selectivity and have similar IC50 values against each cathepsin in cell-based and enzyme assays. The basic inhibitor balicatib has greater cellular potencies than expected on the basis of purified enzyme assays. The accumulation of [14C]-balicatib in fibroblasts is blocked by prior treatment of the cells with NH4Cl, consistent with balicatib having lysosomotropic properties. These results support the use of L-873724 and odanacatib as tools to identify novel roles for Cat K using human cell-based systems, but suggest using caution in the interpretation of studies employing the other compounds.

scholarly journals Mechanical Properties of Native and Cross-linked Type I Collagen Fibrils

2008 ◽  
Vol 94 (6) ◽  
pp. 2204-2211 ◽  
Author(s):  
Lanti Yang ◽  
Kees O. van der Werf ◽  
Carel F.C. Fitié ◽  
Martin L. Bennink ◽  
Pieter J. Dijkstra ◽  
...  
Keyword(s):  
Mechanical Properties ◽  
Type I Collagen ◽  
Collagen Fibrils ◽  
Type I

scholarly journals Regenerative Rehabilitation in Injuries of Tendons

2021 ◽  
Vol 3 (2) ◽  
pp. 192-206
Author(s):  
Sergey G. Sсherbak ◽  
Stanislav V. Makarenko ◽  
Olga V. Shneider ◽  
Tatyana A. Kamilova ◽  
Alexander S. Golota
Keyword(s):  
Mechanical Properties ◽  
Type I Collagen ◽  
Transforming Growth Factor ◽  
Healing Process ◽  
Tendon Healing ◽  
Tendon Injuries ◽  
Type I ◽  
Differentiation Markers ◽  
Postoperative Rehabilitation ◽  
Potent Inducer

The mechanical properties of tendons are thought to be affected by different loading levels. Changes in the mechanical properties of tendons, such as stiffness, have been reported to influence the risk of tendon injuries chiefly in athletes and the elderly, thereby affecting motor function execution. Unloading resulted in reduced tendons stiffness, and resistance exercise exercise counteracts this. Transforming growth factor-1 is a potent inducer of type I collagen and mechanosensitive genes encoding tenogenic differentiation markers expression which play critical roles in tendon tissue formation, tendon healing and their adaptation during exercise. In recent years, our understanding of the molecular biology of tendons growth and repair has expanded. It is probable that the next advance in the treatment of tendon injuries will result from the application of this basic science knowledge and the clinical solution will encompass not only the the best postoperative rehabilitation protocols, but also the optimal biological modulation of the healing process.

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