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      TGFβ activity released from platelet-rich fibrin adsorbs to titanium surface and collagen membranes

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          Abstract

          Platelet-rich fibrin (PRF) contains a broad spectrum of bioactive molecules that can trigger several cellular responses. However, these molecules along with their upstream responses remain mostly uninvestigated. By means of proteomics we revealed that PRF lysates contain more than 650 proteins, being TGF -β one of the few growth factors found. To uncover the major target genes regulated by PRF lysates, gingival fibroblasts were exposed to lysates obtained from PRF membranes followed by a whole genome array. We identified 51 genes strongly regulated by PRF including IL11, NOX4 and PRG4 which are characteristic TGF -β target genes. RT-PCR and immunoassay analysis confirmed the TGF -β receptor I kinase-dependent increased expression of IL11, NOX4 and PRG4. The PRF-derived TGF -β activity was verified by the translocation of Smad2/3 into the nucleus along with the increased phosphorylation of Smad3. Considering that PRF is clinically used in combination with dental implants and collagen membranes, we showed here that PRF-derived TGF -β activity adsorbs to titanium implants and collagen membranes indicated by the changes in gene expression and immunoassay analysis. Our study points towards TGF -β as major target of PRF and suggest that TGF -β activity released by PRF adsorbs to titanium surface and collagen membranes

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          Most cited references46

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          Controlling the False Discovery Rate: A Practical and Powerful Approach to Multiple Testing

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            Platelet-rich fibrin (PRF): a second-generation platelet concentrate. Part III: leucocyte activation: a new feature for platelet concentrates?

            Platelet-rich fibrin (PRF) belongs to a new generation of platelet concentrates, with simplified processing and without biochemical blood handling. In this third article, we investigate the immune features of this biomaterial. During PRF processing, leucocytes could also secrete cytokines in reaction to the hemostatic and inflammatory phenomena artificially induced in the centrifuged tube. We therefore undertook to quantify 5 significant cell mediators within platelet poor plasma supernatant and PRF clot exudate serum: 3 proinflammatory cytokines (IL-1beta, IL-6, and TNF-alpha), an antiinflammatory cytokine (IL-4), and a key growth promoter of angiogenesis (VEGF). Our data are correlated with that obtained in plasma (nonactivated blood) and in sera (activated blood). These initial analyses revealed that PRF could be an immune regulation node with inflammation retrocontrol abilities. This concept could explain the reduction of postoperative infections when PRF is used as surgical additive.
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              Comparative release of growth factors from PRP, PRF, and advanced-PRF.

              The use of platelet concentrates has gained increasing awareness in recent years for regenerative procedures in modern dentistry. The aim of the present study was to compare growth factor release over time from platelet-rich plasma (PRP), platelet-rich fibrin (PRF), and a modernized protocol for PRF, advanced-PRF (A-PRF).
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                Author and article information

                Contributors
                reinhard.gruber@meduniwien.ac.at
                Journal
                Sci Rep
                Sci Rep
                Scientific Reports
                Nature Publishing Group UK (London )
                2045-2322
                23 June 2020
                23 June 2020
                2020
                : 10
                : 10203
                Affiliations
                [1 ]ISNI 0000 0000 9259 8492, GRID grid.22937.3d, Department of Oral Biology, , Medical University of Vienna, ; Vienna, Austria
                [2 ]ISNI 0000 0001 0726 5157, GRID grid.5734.5, Department of Periodontology, School of Dental Medicine, , University of Bern, ; Bern, Switzerland
                [3 ]ISNI 0000 0000 9259 8492, GRID grid.22937.3d, Core Facility Proteomics, Clinical Institute of Laboratory Medicine, , Medical University of Vienna, ; Vienna, Austria
                [4 ]ISNI 0000 0000 9259 8492, GRID grid.22937.3d, Austrian Cluster for Tissue Regeneration, , Medical University of Vienna, ; Vienna, Austria
                [5 ]ISNI 0000 0004 0385 4466, GRID grid.443909.3, Department of Conservative Dentistry, School of Dentistry, , University of Chile, ; Santiago, Chile
                [6 ]ISNI 0000 0004 1937 0650, GRID grid.7400.3, Clinic of Reconstructive Dentistry, , University of Zurich, ; Zurich, Switzerland
                Author information
                http://orcid.org/0000-0003-1964-3965
                http://orcid.org/0000-0001-5400-9009
                http://orcid.org/0000-0002-5832-7327
                Article
                67167
                10.1038/s41598-020-67167-3
                7311486
                cd34314d-41df-4d75-8eef-b01e8e0488d3
                © The Author(s) 2020

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 5 August 2019
                : 26 May 2020
                Funding
                Funded by: FundRef https://doi.org/10.13039/501100007619, Osteology Foundation;
                Award ID: 17-125
                Award ID: 17-125
                Award ID: 17-125
                Award ID: 17-219
                Award ID: 14-126
                Award Recipient :
                Funded by: FundRef https://doi.org/10.13039/501100002428, Austrian Science Fund (Fonds zur Förderung der Wissenschaftlichen Forschung);
                Award ID: 4072-B28
                Award Recipient :
                Categories
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                Custom metadata
                © The Author(s) 2020

                Uncategorized
                cell biology,computational biology and bioinformatics
                Uncategorized
                cell biology, computational biology and bioinformatics

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