Leucocyte- and platelet-rich fibrin regulates expression of genes related to early wound healing in human gingival fibroblasts.
Leucocyte- and platelet-rich fibrin
angiogenesis
fibroblast
gene expression
mitogen-activated protein kinases
Journal
Journal of clinical periodontology
ISSN: 1600-051X
Titre abrégé: J Clin Periodontol
Pays: United States
ID NLM: 0425123
Informations de publication
Date de publication:
07 2020
07 2020
Historique:
received:
22
01
2020
revised:
03
04
2020
accepted:
11
04
2020
pubmed:
19
4
2020
medline:
5
3
2021
entrez:
19
4
2020
Statut:
ppublish
Résumé
Leucocyte- and platelet-rich fibrin (L-PRF) is a blood-derived biomaterial rich in leucocytes and platelets embedded in a high-density fibrin network that can be compressed into a membrane and used in surgical applications to stimulate tissue regeneration and wound healing, especially in oral cavity. This study aimed to determine the combined effects of the growth factors and cells present in L-PRF on fibroblasts that directly face the L-PRF membranes placed during surgical procedures. The effect of L-PRF from six donors on the expression of 84 key wound healing genes in normal human gingival fibroblasts was tested by RT-qPCR. L-PRF significantly regulated the expression of 33 fibroblast genes (39%), including interleukins, myofibroblast-, extracellular matrix- and angiogenesis-associated genes, and matrix metalloproteinase-1 and -3. L-PRF regulated fibroblast gene expression both time- and dose-dependently, and the effects were mediated by mitogen-activated protein kinases ERK1/2, JNK and p38. L-PRF also stimulated fibroblast wound closure and promoted the ability of fibroblasts to induce endothelial tube formation. L-PRF-induced gene expression changes in fibroblast were similar to those observed in early human and pig wounds. This study provides new insights into the biological mechanism by which L-PRF regulates key gingival fibroblast functions important in wound healing.
Sections du résumé
BACKGROUND
Leucocyte- and platelet-rich fibrin (L-PRF) is a blood-derived biomaterial rich in leucocytes and platelets embedded in a high-density fibrin network that can be compressed into a membrane and used in surgical applications to stimulate tissue regeneration and wound healing, especially in oral cavity. This study aimed to determine the combined effects of the growth factors and cells present in L-PRF on fibroblasts that directly face the L-PRF membranes placed during surgical procedures.
METHODS
The effect of L-PRF from six donors on the expression of 84 key wound healing genes in normal human gingival fibroblasts was tested by RT-qPCR.
RESULTS
L-PRF significantly regulated the expression of 33 fibroblast genes (39%), including interleukins, myofibroblast-, extracellular matrix- and angiogenesis-associated genes, and matrix metalloproteinase-1 and -3. L-PRF regulated fibroblast gene expression both time- and dose-dependently, and the effects were mediated by mitogen-activated protein kinases ERK1/2, JNK and p38. L-PRF also stimulated fibroblast wound closure and promoted the ability of fibroblasts to induce endothelial tube formation. L-PRF-induced gene expression changes in fibroblast were similar to those observed in early human and pig wounds.
CONCLUSIONS
This study provides new insights into the biological mechanism by which L-PRF regulates key gingival fibroblast functions important in wound healing.
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
851-862Subventions
Organisme : CIHR
ID : PJT‐153223
Pays : Canada
Informations de copyright
© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
Références
Ågren, M., Rasmussen, K., Pakkenberg, B., & Jørgensen, B. (2014). Growth factor and proteinase profile of Vivostat® platelet-rich fibrin linked to tissue repair. Vox Sanguinis, 107, 37-43.
Anuroopa, P., & Padmavathi Patil, V. K. R. (2014). Role and efficacy of L-PRFmatrix in the regeneration of periodontal defect: A new perspective. Journal of Clinical and Diagnostic Research, 8, ZD03-ZD05.
Barrientos, S., Stojadinovic, O., Golinko, M. S., Brem, H., & Tomic-Canic, M. (2008). Growth factors and cytokines in wound healing. Wound Repair Regen, 16, 585-601.
Bi, J., Koivisto, L., Owen, G., Huang, P., Wang, Z., Shen, Y., … Larjava, H. S. (2016). Epithelial microvesicles promote an inflammatory phenotype in fibroblasts. Journal of Dental Research, 95, 680-688. https://doi.org/10.1177/0022034516633172
Chang, I. C., Tsai, C. H., & Chang, Y. C. (2010). Platelet-rich fibrin modulates the expression of extracellular signal-regulated protein kinase and osteoprotegerin in human osteoblasts. Journal of Biomedical Materials Research, 95, 327-332. https://doi.org/10.1002/jbm.a.32839
Chellini, F., Tani, A., Vallone, L., Nosi, D., Pavan, P., Bambi, F., … Sassoli, C. (2018). Platelet-rich plasma prevents in vitro transforming growth factor-beta1-induced fibroblast to myofibroblast transition: involvement of vascular endothelial growth factor (VEGF)-A/VEGF receptor-1-mediated signaling (dagger). Cells, 7, E142.
Choukroun, J., Diss, A., Simonpieri, A., Girard, M. O., Schoeffler, C., Dohan, S. L., … Dohan, D. M. (2006). Platelet-rich fibrin (PRF): A second-generation platelet concentrate. Part IV: Clinical effects on tissue healing. Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology and Endodontics, 101, e56-e60.
Dang, C. M., Beanes, S. R., Lee, H., Zhang, X., Soo, C., & Ting, K. (2003). Scarless fetal wounds are associated with an increased matrix metalloproteinase-to-tissue-derived inhibitor of metalloproteinase ratio. Plastic and Reconstructive Surgery, 111, 2273-2285. https://doi.org/10.1097/01.PRS.0000060102.57809.DA
Derynck, R., & Zhang, Y. E. (2003). Smad-dependent and Smad-independent pathways in TGF-β family signalling. Nature, 425, 577. https://doi.org/10.1038/nature02006
Desmoulière, A., Geinoz, A., Gabbiani, F., & Gabbiani, G. (1993). Transforming growth factor-beta 1 induces alpha-smooth muscle actin expression in granulation tissue myofibroblasts and in quiescent and growing cultured fibroblasts. The Journal of Cell Biology, 122, 103-111. https://doi.org/10.1083/jcb.122.1.103
Dohan, D. M., Choukroun, J., Diss, A., Dohan, S. L., Dohan, A. J., Mouhyi, J., & Gogly, B. (2006a). Platelet-rich fibrin (PRF): A second-generation platelet concentrate. Part II: Platelet-related biologic features. Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology and Endodontics, 101, e45-e50. https://doi.org/10.1016/j.tripleo.2005.07.009
Dohan, D. M., Choukroun, J., Diss, A., Dohan, S. L., Dohan, A. J., Mouhyi, J., & Gogly, B. (2006b). Platelet-rich fibrin (PRF): A second-generation platelet concentrate. Part III: Leucocyte activation: A new feature for platelet concentrates? Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology and Endodontics, 101, e51-55. https://doi.org/10.1016/j.tripleo.2005.07.010
Dohan Ehrenfest, D. M., Del Corso, M., Diss, A., Mouhyi, J., & Charrier, J.-B. (2010). Three-dimensional architecture and cell composition of a Choukroun's platelet-rich fibrin clot and membrane. Journal of Periodontology, 81, 546-555. https://doi.org/10.1902/jop.2009.090531
Dohan Ehrenfest, D. M., Pinto, N. R., Pereda, A., Jiménez, P., Corso, M. D., Kang, B.-S., … Quirynen, M. (2018). The impact of the centrifuge characteristics and centrifugation protocols on the cells, growth factors, and fibrin architecture of a leukocyte-and platelet-rich fibrin (L-PRF) clot and membrane. Platelets, 29, 171-184. https://doi.org/10.1080/09537104.2017.1293812
Dufour, A., & Overall, C. M. (2013). Missing the target: Matrix metalloproteinase antitargets in inflammation and cancer. Trends in Pharmacological Sciences, 34, 233-242. https://doi.org/10.1016/j.tips.2013.02.004
Ehrenfest, D. M. D., Diss, A., Odin, G., Doglioli, P., Hippolyte, M.-P., & Charrier, J.-B. (2009). In vitro effects of Choukroun's PRF (platelet-rich fibrin) on human gingival fibroblasts, dermal prekeratinocytes, preadipocytes, and maxillofacial osteoblasts in primary cultures. Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology, and Endodontology, 108, 341-352. https://doi.org/10.1016/j.tripleo.2009.04.020
Florin, L., Maas-Szabowski, N., Werner, S., Szabowski, A., & Angel, P. (2005). Increased keratinocyte proliferation by JUN-dependent expression of PTN and SDF-1 in fibroblasts. Journal of Cell Science, 118, 1981-1989. https://doi.org/10.1242/jcs.02303
Gaßling, V. L., Açil, Y., Springer, I. N., Hubert, N., & Wiltfang, J. (2009). Platelet-rich plasma and platelet-rich fibrin in human cell culture. Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology, and Endodontology, 108, 48-55. https://doi.org/10.1016/j.tripleo.2009.02.007
Graves, D. T., Nooh, N., Gillen, T., Davey, M., Patel, S., Cottrell, D., & Amar, S. (2001). IL-1 plays a critical role in oral, but not dermal, wound healing. The Journal of Immunology, 167, 5316-5320. https://doi.org/10.4049/jimmunol.167.9.5316
Häkkinen, L., Hildebrand, H. C., Berndt, A., Kosmehl, H., & Larjava, H. (2000). Immunolocalization of tenascin-C, alpha9 integrin subunit, and alphavbeta6 integrin during wound healing in human oral mucosa. Journal of Histochemistry and Cytochemistry, 48, 985-998.
Häkkinen, L., Larjava, H., & Fournier, B. P. (2014). Distinct phenotype and therapeutic potential of gingival fibroblasts. Cytotherapy, 16, 1171-1186. https://doi.org/10.1016/j.jcyt.2014.04.004
Harty, M., Neff, A. W., King, M. W., & Mescher, A. L. (2003). Regeneration or scarring: An immunologic perspective. Developmental Dynamics, 226, 268-279. https://doi.org/10.1002/dvdy.10239
Hinz, B., Pittet, P., Smith-Clerc, J., Chaponnier, C., & Meister, J. J. (2004). Myofibroblast development is characterized by specific cell-cell adherens junctions. Molecular Biology of the Cell, 15, 4310-4320. https://doi.org/10.1091/mbc.e04-05-0386
Honardoust, D., Eslami, A., Larjava, H., & Häkkinen, L. (2008). Localization of small leucine-rich proteoglycans and transforming growth factor-beta in human oral mucosal wound healing. Wound Repair Regen, 16, 814-823.
Huang, P., Bi, J., Owen, G. R., Chen, W., Rokka, A., Koivisto, L., … Larjava, H. (2015). Keratinocyte microvesicles regulate the expression of multiple genes in dermal fibroblasts. The Journal of Investigative Dermatology, 135, 3051-3059. https://doi.org/10.1038/jid.2015.320
Jain, V., Triveni, M. G., Kumar, A. B., & Mehta, D. S. (2012). Role of platelet-rich-fibrin in enhancing palatal wound healing after free graft. Contemporary Clinical Dentistry, 3, S240-S243.
Johnson, K. E., & Wilgus, T. A. (2014). Vascular endothelial growth factor and angiogenesis in the regulation of cutaneous wound repair. Advances in Wound Care, 3, 647-661. https://doi.org/10.1089/wound.2013.0517
Kudo, A. (2011). Periostin in fibrillogenesis for tissue regeneration: Periostin actions inside and outside the cell. Cellular and Molecular Life Sciences, 68, 3201-3207. https://doi.org/10.1007/s00018-011-0784-5
Larjava, H. (2012). Oral wound healing: Cell biology and clinical management. Hoboken, NJ: John Wiley & Sons.
Lu, P., Takai, K., Weaver, V. M., & Werb, Z. (2011). Extracellular matrix degradation and remodeling in development and disease. Cold Spring Harb Perspect Biol, 3(12), a005058. https://doi.org/10.1101/cshperspect.a005058
Mak, K., Manji, A., Gallant-Behm, C., Wiebe, C., Hart, D. A., Larjava, H., & Häkkinen, L. (2009). Scarless healing of oral mucosa is characterized by faster resolution of inflammation and control of myofibroblast action compared to skin wounds in the red Duroc pig model. Journal of Dermatological Science, 56, 168-180. https://doi.org/10.1016/j.jdermsci.2009.09.005
Marenzi, G., Riccitiello, F., Tia, M., di Lauro, A., & Sammartino, G. (2015). Influence of leukocyte- and platelet-rich fibrin (L-PRF) in the healing of simple postextraction sockets: a split-mouth study. BioMed Research International, 2015, 369273. https://doi.org/10.1155/2015/369273
McFarland-Mancini, M. M., Funk, H. M., Paluch, A. M., Zhou, M., Giridhar, P. V., Mercer, C. A., … Drew, A. F. (2010). Differences in wound healing in mice with deficiency of IL-6 versus IL-6 receptor. The Journal of Immunology, 184, 7219-7228. https://doi.org/10.4049/jimmunol.0901929
Mortier, A., Gouwy, M., Van Damme, J., & Proost, P. (2011). Effect of posttranslational processing on the in vitro and in vivo activity of chemokines. Experimental Cell Research, 317, 642-654. https://doi.org/10.1016/j.yexcr.2010.11.016
Overall, C. M., & Kleifeld, O. (2006). Tumour microenvironment - opinion: Validating matrix metalloproteinases as drug targets and anti-targets for cancer therapy. Nature Reviews Cancer, 6, 227-239. https://doi.org/10.1038/nrc1821
Page-McCaw, A., Ewald, A. J., & Werb, Z. (2007). Matrix metalloproteinases and the regulation of tissue remodelling. Nature Reviews Molecular Cell Biology, 8, 221-233. https://doi.org/10.1038/nrm2125
Polley, M.-Y., Leung, S. C. Y., McShane, L. M., Gao, D., Hugh, J. C., Mastropasqua, M. G., … Nielsen, T. O. (2013). An international Ki67 reproducibility study. JNCI Journal of the National Cancer Institute, 105, 1897-1906. https://doi.org/10.1093/jnci/djt306
Rennekampff, H. O., Hansbrough, J. F., Kiessig, V., Dore, C., Sticherling, M., & Schroder, J. M. (2000). Bioactive interleukin-8 is expressed in wounds and enhances wound healing. Journal of Surgical Research, 93, 41-54. https://doi.org/10.1006/jsre.2000.5892
Repnik, U., Starr, A. E., Overall, C. M., & Turk, B. (2015). Cysteine cathepsins activate ELR chemokines and inactivate non-ELR chemokines. Journal of Biological Chemistry, 290, 13800-13811. https://doi.org/10.1074/jbc.M115.638395
Roberts, A. B., McCune, B. K., & Sporn, M. B. (1992). TGF-β: Regulation of extracellular matrix. Kidney International, 41, 557-559. https://doi.org/10.1038/ki.1992.81
Rodriguez, D., Morrison, C. J., & Overall, C. M. (2010). Matrix metalloproteinases: What do they not do? New substrates and biological roles identified by murine models and proteomics. Biochimica Et Biophysica Acta, 1803, 39-54. https://doi.org/10.1016/j.bbamcr.2009.09.015
Roy, S., Driggs, J., Elgharably, H., Biswas, S., Findley, M., Khanna, S., … Sen, C. K. (2011). Platelet-rich fibrin matrix improves wound angiogenesis via inducing endothelial cell proliferation. Wound Repair and Regeneration, 19, 753-766. https://doi.org/10.1111/j.1524-475X.2011.00740.x
Sánchez, M., Anitua, E., Orive, G., Mujika, I., & Andia, I. (2009). Platelet-rich therapies in the treatment of orthopaedic sport injuries. Sports Medicine, 39, 345-354. https://doi.org/10.2165/00007256-200939050-00002
Sapudom, J., Rubner, S., Martin, S., Thoenes, S., Anderegg, U., & Pompe, T. (2015). The interplay of fibronectin functionalization and TGF-beta1 presence on fibroblast proliferation, differentiation and migration in 3D matrices. Biomater Sci, 3, 1291-1301.
Schar, M. O., Diaz-Romero, J., Kohl, S., Zumstein, M. A., & Nesic, D. (2015). Platelet-rich concentrates differentially release growth factors and induce cell migration in vitro. Clinical Orthopaedics and Related Research, 473, 1635-1643. https://doi.org/10.1007/s11999-015-4192-2
Serini, G., Bochaton-Piallat, M. L., Ropraz, P., Geinoz, A., Borsi, L., Zardi, L., & Gabbiani, G. (1998). The fibronectin domain ED-A is crucial for myofibroblastic phenotype induction by transforming growth factor-beta1. Journal of Cell Biology, 142, 873-881.
Su, C. Y., Kuo, Y. P., Tseng, Y. H., Su, C. H., & Burnouf, T. (2009). In vitro release of growth factors from platelet-rich fibrin (PRF): A proposal to optimize the clinical applications of PRF. Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology and Endodontics, 108, 56-61. https://doi.org/10.1016/j.tripleo.2009.02.004
Tsai, C.-H., Shen, S.-Y., Zhao, J.-H., & Chang, Y.-C. (2009). Platelet-rich fibrin modulates cell proliferation of human periodontally related cells in vitro. Journal of Dental Sciences, 4, 130-135. https://doi.org/10.1016/S1991-7902(09)60018-0
Weibrich, G., Kleis, W. K., & Hafner, G. (2002a). Growth factor levels in the platelet-rich plasma produced by 2 different methods: Curasan-type PRP kit versus PCCS PRP system. International Journal of Oral & Maxillofacial Implants, 17, 184-190.
Weibrich, G., Kleis, W. K., Hafner, G., & Hitzler, W. E. (2002b). Growth factor levels in platelet-rich plasma and correlations with donor age, sex, and platelet count. Journal of cranio-maxillo-facial Surgery, 30, 97-102. https://doi.org/10.1054/jcms.2002.0285
Westermarck, J., Li, S. P., Kallunki, T., Han, J., & Kähäri, V. M. (2001). p38 mitogen-activated protein kinase-dependent activation of protein phosphatases 1 and 2A inhibits MEK1 and MEK2 activity and collagenase 1 (MMP-1) gene expression. Molecular and Cellular Biology, 21, 2373-2383. https://doi.org/10.1128/MCB.21.7.2373-2383.2001
Wong, J. W., Gallant-Behm, C., Wiebe, C., Mak, K., Hart, D. A., Larjava, H., & Häkkinen, L. (2009). Wound healing in oral mucosa results in reduced scar formation as compared with skin: Evidence from the red Duroc pig model and humans. Wound Repair and Regeneration, 17, 717-729. https://doi.org/10.1111/j.1524-475X.2009.00531.x
Yancopoulos, G. D., Davis, S., Gale, N. W., Rudge, J. S., Wiegand, S. J., & Holash, J. (2000). Vascular-specific growth factors and blood vessel formation. Nature, 407, 242. https://doi.org/10.1038/35025215
Yates, C. C., Hebda, P., & Wells, A. (2012). Skin wound healing and scarring: Fetal wounds and regenerative restitution. Birth Defects Research Part C: Embryo Today: Reviews, 96, 325-333. https://doi.org/10.1002/bdrc.21024