TGFβ Activity Released from Platelet-rich Fibrin Adsorbs to Titanium Surface and Collagen Membranes

Overview

Journal Sci Rep

Specialty Science

Date 2020 Jun 25

PMID 32576959

Citations 20

Authors

Francesca Di Summa

Zahra Kargarpour

Jila Nasirzade

Alexandra Stahli

Goran Mitulovic

Tanja Panic-Jankovic

Veronika Koller

Cosima Kaltenbach

Heinz Muller

Layla Panahipour

Reinhard Gruber

Franz-Josef Strauss

Affiliations

Soon will be listed here.

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.

Citing Articles

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References

Nevins M, Kao R, McGuire M, McClain P, Hinrichs J, McAllister B . Platelet-derived growth factor promotes periodontal regeneration in localized osseous defects: 36-month extension results from a randomized, controlled, double-masked clinical trial. J Periodontol. 2012; 84(4):456-64. PMC: 5715458. DOI: 10.1902/jop.2012.120141. View

Dohan D, Choukroun J, Diss A, Dohan S, Dohan A, Mouhyi J . Platelet-rich fibrin (PRF): a second-generation platelet concentrate. Part I: technological concepts and evolution. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2006; 101(3):e37-44. DOI: 10.1016/j.tripleo.2005.07.008. View

Temmerman A, Vandessel J, Castro A, Jacobs R, Teughels W, Pinto N . The use of leucocyte and platelet-rich fibrin in socket management and ridge preservation: a split-mouth, randomized, controlled clinical trial. J Clin Periodontol. 2016; 43(11):990-999. DOI: 10.1111/jcpe.12612. View

Dohan Ehrenfest D, Doglioli P, de Peppo G, Del Corso M, Charrier J . Choukroun's platelet-rich fibrin (PRF) stimulates in vitro proliferation and differentiation of human oral bone mesenchymal stem cell in a dose-dependent way. Arch Oral Biol. 2010; 55(3):185-94. DOI: 10.1016/j.archoralbio.2010.01.004. View

Wang X, Zhang Y, Choukroun J, Ghanaati S, Miron R . Effects of an injectable platelet-rich fibrin on osteoblast behavior and bone tissue formation in comparison to platelet-rich plasma. Platelets. 2017; 29(1):48-55. DOI: 10.1080/09537104.2017.1293807. View

Setzer F, Oberle V, Blass M, Moller E, Russwurm S, Deigner H . Platelet-derived microvesicles induce differential gene expression in monocytic cells: a DNA microarray study. Platelets. 2006; 17(8):571-6. DOI: 10.1080/09537100600760244. View

Burnouf T, Strunk D, Koh M, Schallmoser K . Human platelet lysate: Replacing fetal bovine serum as a gold standard for human cell propagation?. Biomaterials. 2015; 76:371-87. DOI: 10.1016/j.biomaterials.2015.10.065. View

Nishimoto S, Fujita K, Sotsuka Y, Kinoshita M, Fujiwara T, Kawai K . Growth Factor Measurement and Histological Analysis in Platelet Rich Fibrin: A Pilot Study. J Maxillofac Oral Surg. 2015; 14(4):907-13. PMC: 4648775. DOI: 10.1007/s12663-015-0768-3. View

Kobayashi E, Fluckiger L, Fujioka-Kobayashi M, Sawada K, Sculean A, Schaller B . Comparative release of growth factors from PRP, PRF, and advanced-PRF. Clin Oral Investig. 2016; 20(9):2353-2360. DOI: 10.1007/s00784-016-1719-1. View

10.

Burkhart J, Gambaryan S, Watson S, Jurk K, Walter U, Sickmann A . What can proteomics tell us about platelets?. Circ Res. 2014; 114(7):1204-19. DOI: 10.1161/CIRCRESAHA.114.301598. View

11.

Strauss F, Di Summa F, Stahli A, Matos L, Vaca F, Schuldt G . TGF-β activity in acid bone lysate adsorbs to titanium surface. Clin Implant Dent Relat Res. 2019; 21(2):336-343. PMC: 6593995. DOI: 10.1111/cid.12734. View

12.

Stahli A, Miron R, Bosshardt D, Sculean A, Gruber R . Collagen Membranes Adsorb the Transforming Growth Factor-β Receptor I Kinase-Dependent Activity of Enamel Matrix Derivative. J Periodontol. 2016; 87(5):583-90. DOI: 10.1902/jop.2016.150538. View

13.

Strauss F, Stahli A, Beer L, Mitulovic G, Gilmozzi V, Haspel N . Acid bone lysate activates TGFβ signalling in human oral fibroblasts. Sci Rep. 2018; 8(1):16065. PMC: 6207660. DOI: 10.1038/s41598-018-34418-3. View

14.

Stahli A, Bosshardt D, Sculean A, Gruber R . Emdogain-regulated gene expression in palatal fibroblasts requires TGF-βRI kinase signaling. PLoS One. 2014; 9(9):e105672. PMC: 4157743. DOI: 10.1371/journal.pone.0105672. View

15.

Panda S, Sankari M, Satpathy A, Jayakumar D, Mozzati M, Mortellaro C . Adjunctive Effect of Autologus Platelet-Rich Fibrin to Barrier Membrane in the Treatment of Periodontal Intrabony Defects. J Craniofac Surg. 2016; 27(3):691-6. DOI: 10.1097/SCS.0000000000002524. View

16.

Hempel U, Hintze V, Moller S, Schnabelrauch M, Scharnweber D, Dieter P . Artificial extracellular matrices composed of collagen I and sulfated hyaluronan with adsorbed transforming growth factor β1 promote collagen synthesis of human mesenchymal stromal cells. Acta Biomater. 2011; 8(2):659-66. DOI: 10.1016/j.actbio.2011.10.026. View

17.

Augustin G, Davila S, Mihoci K, Udiljak T, Vedrina D, Antabak A . Thermal osteonecrosis and bone drilling parameters revisited. Arch Orthop Trauma Surg. 2007; 128(1):71-7. DOI: 10.1007/s00402-007-0427-3. View

18.

Bakker A, Klein-Nulend J . Osteoblast isolation from murine calvaria and long bones. Methods Mol Biol. 2011; 816:19-29. DOI: 10.1007/978-1-61779-415-5_2. View

19.

Rosen D, Stempien S, Thompson A, Seyedin S . Transforming growth factor-beta modulates the expression of osteoblast and chondroblast phenotypes in vitro. J Cell Physiol. 1988; 134(3):337-46. DOI: 10.1002/jcp.1041340304. View

20.

Stein G, Lian J, Owen T . Relationship of cell growth to the regulation of tissue-specific gene expression during osteoblast differentiation. FASEB J. 1990; 4(13):3111-23. DOI: 10.1096/fasebj.4.13.2210157. View