Oligomeric proanthocyanidins released from dentin induce regenerative dental pulp cell response.

Published on Jun 1, 2017in Acta Biomaterialia8.947
· DOI :10.1016/J.ACTBIO.2017.03.051
Daniel Kulakowski2
Estimated H-index: 2
(UIC: University of Illinois at Chicago),
A.A. Leme-Kraus9
Estimated H-index: 9
(UIC: University of Illinois at Chicago)
+ 5 AuthorsAnakarina B. Bedran-Russo21
Estimated H-index: 21
(UIC: University of Illinois at Chicago)
Sources
Abstract
Abstract Proanthocyanidins (PACs) are plant-derived, multifunctional compounds that possess high interactivity with extracellular matrix (ECM) components. The documented affinity of PACs for type-I collagen is directly correlated with their structural features and degree of polymerization. In this investigation, centrifugal partition chromatography (CPC) was used to sequentially deplete less active monomeric and polymeric PACs from a crude Pinus massoniana bark extract to create refined mixtures enriched in oligomeric PACs. The ability of these oligomeric PACs to modify the mechanical properties of the dentin collagen matrix and their biocompatibility with dental pulp cells (DPCs) was evaluated in an innovative biomimetic environment. The refined mixtures displayed high interactivity with dentin collagen as demonstrated by a significant increase (>5-fold) in the modulus of elasticity of the dentin matrix. In a simplified model of the dentin-DPC complex, DPCs embedded within their native ECM in the presence of PAC-treated dentin exhibited increased proliferation. Quantitative gene expression analyses indicated that exposure to PAC-treated dentin increased the expression of key biomineralization and odontogenic differentiation regulators, including RUNX2, BMP2, OCN, and DSPP. LC-MS/MS analysis revealed that PACs two to four units long (dimers, trimers, and tetramers) were being released from dentin into media, influencing cell behavior. Overall, the results suggested that PAC dimers, trimers, and tetramers are not only biocompatible, but enhance the differentiation of DPCs towards a phenotype that favors biomineralization. PAC-enriched refined mixtures can influence the field of biomaterials and regeneration by serving as renewable, non-cytotoxic agents that can increase the mechanical properties of biomaterials. Statement of Significance Pine bark extract is a renewable source of structurally diverse proanthocyanidins (PACs), multifunctional compounds whose interaction with collagen can be tailored to specific purposes by enrichment of selected PACs from the complex mixture. Oligomeric PACs were enriched from the extract and were shown here to sustain desired tissue modification and were thus assessed for cellular response in a model of the dentin-pulp interface. This model was developed to mimic leaching of potentially reactive compounds into pulp tissue. Dental pulp cells exposed to PAC-treated dentin showed increased proliferation and expression of genes necessary for extracellular matrix deposition and biomineralization, processes crucial for forming new dentin. Thus, collagen-interactive PACs may also enhance tissue regeneration and have broad impact in tissue engineering.
📖 Papers frequently viewed together
2000
3 Authors (Wei Tan, R. Krishnaraj)
References31
Newest
#1Joo-Won Nam (UIC: University of Illinois at Chicago)H-Index: 21
#2RS Phansalkar (UIC: University of Illinois at Chicago)H-Index: 12
Last. Guido F. PauliH-Index: 64
view all 12 authors...
The ability of certain oligomeric proanthocyanidins (OPACs) to enhance the biomechanical properties of dentin involves collagen cross-linking of the 1.3–4.5 nm wide space via protein–polyphenol interactions. A systematic interdisciplinary search for the bioactive principles of pine bark has yielded the trimeric PAC, ent-epicatechin-(4β→8)-epicatechin-(2β→O→7,4β→8)-catechin (3), representing the hitherto most potent single chemical entity capable of enhancing dentin stiffness. Building the case f...
Source
#1Tadashi Nakanishi (University of Tokushima)H-Index: 18
#2Kayo Mukai (University of Tokushima)H-Index: 5
Last. Takashi Matsuo (University of Tokushima)H-Index: 30
view all 5 authors...
Aim To investigate the effect of catechins on vascular endothelial growth factor (VEGF) production and cyclooxygenase-2 (COX-2) expression in human dental pulp cells (HDPC) stimulated with bacteria-derived factors or pro-inflammatory cytokines. Methodology Morphologically fibroblastic cells established from explant cultures of healthy human dental pulp tissues were used as HDPC. HDPC pre-treated with catechins, epigallocatechin-3-gallate (EGCG) or epicatechin gallate (ECG), were exposed to lipop...
Source
#1RS Phansalkar (UIC: University of Illinois at Chicago)H-Index: 12
#2Joo-Won Nam (UIC: University of Illinois at Chicago)H-Index: 21
Last. Guido F. Pauli (UIC: University of Illinois at Chicago)H-Index: 64
view all 10 authors...
Abstract Grape seeds are a rich source of polyphenols, especially proanthocyanidins (PACs), and are also known for the presence of galloylated oligomeric PACs (OPACs). The present study focuses on the phytochemical methodology for grape seed (O)PACs and their potential role as dentin biomodifiers to be used in restorative and reparative dentistry. A new method using centrifugal partition chromatography (CPC) was developed for the preparative separation of the grape seed (O)PACs. Orthogonal phyto...
Source
#1D.L.S. Scheffel (UNESP: Sao Paulo State University)H-Index: 8
#2L. Bianchi (UNESP: Sao Paulo State University)H-Index: 4
Last. Josimeri Hebling (UNESP: Sao Paulo State University)H-Index: 54
view all 8 authors...
Clinical Relevance Carbodiimide (EDC) and glutaraldehyde are cross-linking agents capable of increasing resin-dentin bond durability. This study showed that these substances might be safely applied on acid-etched dentin since they have no transdentinal cytotoxic effects on cultured odontoblast-like cells.
Source
#1Sandra V. Verstraeten (CONICET: National Scientific and Technical Research Council)H-Index: 28
#2Cesar G. Fraga (UBA: University of Buenos Aires)H-Index: 68
Last. Patricia I. Oteiza (UC Davis: University of California, Davis)H-Index: 64
view all 3 authors...
Flavonoids are a type of phenolic compound widely present in edible plants. A great number of health benefits have been ascribed to flavonoid consumption in the human population. However, the molecular mechanisms involved in such effects remain to be identified. The flavan-3-ols (−)-epicatechin and (+)-catechin, and their related oligomers (procyanidins) have been thoroughly studied because of their capacity to interact with cell membranes. Starting with these interactions, procyanidins could mo...
Source
#1Cristina de Mattos Pimenta Vidal (UIC: University of Illinois at Chicago)H-Index: 19
#2A.A. Leme (UIC: University of Illinois at Chicago)H-Index: 8
Last. Anakarina B. Bedran-RussoH-Index: 21
view all 10 authors...
Proanthocyanidins (PACs) are secondary plant metabolites that mediate nonenzymatic collagen cross-linking and enhance the properties of collagen based tissue, such as dentin. The extent and nature of cross-linking is influenced by the composition and specific chemical structure of the bioactive compounds present in certain PAC-rich extracts. This study investigated the effect of the molecular weight and stereochemistry of polyphenol compounds on two important properties of dentin, biomechanics, ...
Source
#1René F. Ramos Alvarenga (UIC: University of Illinois at Chicago)H-Index: 7
#2J. Brent FriesenH-Index: 22
Last. Shao-Nong ChenH-Index: 47
view all 10 authors...
This study introduces a flexible and compound targeted approach to Deplete and Enrich Select Ingredients to Generate Normalized Extract Resources, generating DESIGNER extracts, by means of chemical subtraction or augmentation of metabolites. Targeting metabolites based on their liquid–liquid partition coefficients (K values), K targeting uses countercurrent separation methodology to remove single or multiple compounds from a chemically complex mixture, according to the following equation: DESIGN...
Source
#1Francesca Gattazzo (UNIPD: University of Padua)H-Index: 7
#2Anna Urciuolo (UNIPD: University of Padua)H-Index: 14
Last. Paolo Bonaldo (UNIPD: University of Padua)H-Index: 66
view all 3 authors...
Background Extracellular matrix (ECM) is a dynamic and complex environment characterized by biophysical, mechanical and biochemical properties specific for each tissue and able to regulate cell behavior. Stem cells have a key role in the maintenance and regeneration of tissues and they are located in a specific microenvironment, defined as niche.
Source
#1T.R. Aguiar (UIC: University of Illinois at Chicago)H-Index: 13
#2Cristina de Mattos Pimenta Vidal (UIC: University of Illinois at Chicago)H-Index: 19
Last. A.B. Bedran-Russo (UIC: University of Illinois at Chicago)H-Index: 20
view all 9 authors...
Although proanthocyanidins (PACs) modify dentin, the effectiveness of different PAC sources and the correlation with their specific chemical composition are still unknown. This study describes the chemical profiling of natural PAC-rich extracts from 7 plants using ultra high pressure/performance liquid chromatography (UHPLC) to determine the overall composition of these extracts and, in parallel, comprehensively evaluate their effect on dentin properties. The total polyphenol content of the extr...
Source
#1Sriram Ravindran (UIC: University of Illinois at Chicago)H-Index: 22
#2Chun-Chieh Huang (UIC: University of Illinois at Chicago)H-Index: 14
Last. Anne George (UIC: University of Illinois at Chicago)H-Index: 53
view all 3 authors...
Dental Caries affects approximately 90% of the world’s population. At present, the clinical treatment for dental caries is root canal therapy. This treatment results in loss of tooth sensitivity and vitality. Tissue engineering can potentially solve this problem by enabling regeneration of a functional pulp tissue. Dental pulp stem cells (DPSCs) have been shown to be an excellent source for pulp regeneration. However, limited availability of these cells hinders its potential for clinical transla...
Source
Cited By12
Newest
#1Mohsen YazdanianH-Index: 8
Last. Mahdi Rahbar (Ardabil University of Medical Sciences)H-Index: 6
view all 9 authors...
Source
#1Wayne E. ZellerH-Index: 8
Source
#1Berdan Aydin (UIC: University of Illinois at Chicago)H-Index: 10
#2Anne-Ashley Compton (UIC: University of Illinois at Chicago)
Last. Anakarina B. Bedran-Russo (UIC: University of Illinois at Chicago)H-Index: 21
view all 6 authors...
Abstract Purpose Dentin endogenous proteases are involved in the progression of dental caries. This study investigated the proteolytic activity of endogenous enzymes of carious and sound dentin of primary teeth and the potential selective inhibitory effect of plant-derived proanthocyanidins (PACs). Methods Carious and sound dentin from forty extracted primary teeth were collected and cryo-pulverized into a fine powder. Two PAC mixtures were prepared from grape seeds (Vitis vinifera, Vv), an olig...
Source
#2Mariana Reis (UIC: University of Illinois at Chicago)H-Index: 2
OBJECTIVES To develop a protocol for assessment of the bulk viscoelastic behavior of dentin extracellular matrix (ECM), and to assess relationships between induced collagen cross-linking and viscoelasticity of the dentin ECM. METHODS Dentin ECM was treated with agents to induce exogenous collagen cross-linking: proanthocyanidins (PACs) from Vitis vinifera - VVe, PACs from Pinus massoniana - PMe, glutaraldehyde - (GA), or kept untreated (control). A dynamic mechanical strain sweep method was carr...
Source
#1Lívia Tosi Trevelin (UIC: University of Illinois at Chicago)H-Index: 6
#2Yvette Alania (UIC: University of Illinois at Chicago)H-Index: 8
Last. Anakarina B. Bedran-Russo (UIC: University of Illinois at Chicago)H-Index: 21
view all 7 authors...
Abstract Objectives Proanthocyanidins (PACs) are biocompounds mimicking native collagen cross-links. The effective and practical delivery of any biocompound is pivotal for clinical usage. The aim was to investigate the dentin biomodification and effective formation of dentin-resin biointerfaces of two highly bioactive PAC-rich extracts, Vitis vinifera Vv and Camellia sinensis Cs), delivered using neutral (NP) or acidic (AP) rinse-out primer approaches. Methods The depth of dentin demineralizatio...
Source
#1Giulia Orlandi (UNIPV: University of Pavia)H-Index: 3
#2Elia Bari (UNIPV: University of Pavia)H-Index: 13
Last. Sara Perteghella (UNIPV: University of Pavia)H-Index: 20
view all 10 authors...
Mesenchymal stem/stromal cells (MSCs) are a therapeutic target to promote tissue regeneration, mainly when oxidative stress-mediated damage is involved in disease pathogenesis. Here, slow-release silk sericin nanoparticles (SNPs) loaded with natural antioxidant polyphenols were developed to sustain regeneration by tissue-resident MSCs. SNPs were prepared by exploiting a self-assembly method with poloxamer and were loaded with proanthocyanidins (P), quercetin (Q) or epigallocatechin gallate (E). ...
Source
Studies on plant and food phytochemistry and its potential benefits to human health are becoming the focus of the research community. Researchers are turning to alternatives drugs in treating human diseases using natural products from plants and foods. Polyphenols are one of the largest groups in the plant family and consist of many subgroups. One of them is catechin, which is generally acknowledged to be part of a compound in tea. Over the years, investigations have shown that catechin has anti...
Source
#6José Rino Neto (UFG: Universidade Federal de Goiás)H-Index: 2
Research regarding polyphenols has gained prominence over the years because of their potential as pharmacological nutrients. Most polyphenols are flavanols, commonly known as catechins, which are present in high amounts in green tea. Catechins have been found to be promising candidates in the field of biomedicine. The health benefits of catechins, notably their antioxidant effects, are related to their chemical structure and the total number of hydroxyl groups. In addition, catechins possess str...
Source
#1Jonas Halver (Technical University of Dortmund)H-Index: 2
#2Kristin WenzelH-Index: 5
Last. Dennis Schade (CAU: University of Kiel)H-Index: 15
view all 12 authors...
Extracts from the leaves and flowers of Crataegus spp. (i.e., hawthorn species) have been traditionally used with documented preclinical and clinical activities in cardiovascular medicine. Based on reported positive effects on heart muscle after ischemic injury and the overall cardioprotective profile, the present study addressed potential contributions of Crataegus extracts to cardiopoietic differentiation from stem cells. The quantified Crataegus extract WS®1442 stimulated cardiomyogenesis fro...
Source
#1Li Shanji (JLU: Jilin University)H-Index: 3
#2Wai-Ching Liu (NTUT: National Taipei University of Technology)H-Index: 11
Last. Ren-Jei Chung (NTUT: National Taipei University of Technology)H-Index: 11
view all 7 authors...
Abstract In this study, type I collagen membranes were prepared using oligomeric proanthocyanidins (OPCs) as the cross-linking agent. The fabricated materials were evaluated to be applied as guided tissue regeneration membranes for periodontal defects. The mechanical strength of the cross-linked collagen membranes, namely OPCs-Col films, using different concentrations of OPCs ranged from 30 to 60 kPa. The cross-linked collagen membranes had better thermal stability than non-cross-linked one and ...
Source
This website uses cookies.
We use cookies to improve your online experience. By continuing to use our website we assume you agree to the placement of these cookies.
To learn more, you can find in our Privacy Policy.