Platelet‑rich fibrin increases the osteoprotegerin/receptor activator of nuclear factor‑κB ligand ratio in osteoblasts

Sumida,Ryuta; Maeda,Toyonobu; Kawahara,Ichiro; Yusa,Junko; Kato,Yasumasa

doi:10.3892/etm.2019.7560

Platelet‑rich fibrin increases the osteoprotegerin/receptor activator of nuclear factor‑κB ligand ratio in osteoblasts

Authors:
- Ryuta Sumida
- Toyonobu Maeda
- Ichiro Kawahara
- Junko Yusa
- Yasumasa Kato
View Affiliations

Affiliations: Department of Oral and Maxillofacial Surgery, Ohu University School of Dentistry, Koriyama, Fukushima 963‑8611, Japan, Department of Oral Function and Molecular Biology, Ohu University School of Dentistry, Koriyama, Fukushima 963‑8611, Japan, Department of Oral Medical Sciences, Ohu University School of Dentistry, Koriyama, Fukushima 963‑8611, Japan
Published online on: May 8, 2019 https://doi.org/10.3892/etm.2019.7560
Pages: 358-365
Copyright: © Sumida et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Platelet‑rich fibrin (PRF) is a platelet concentrate derived from complete autologous blood rich in growth factors in the fibrin matrix. Although PRF has been used during oral surgery to optimize wound healing in soft and hard tissue, the precise role of PRF in bone healing remains unclear. The present study assessed the role of PRF in bone remodeling. PRF was prepared from whole blood by low speed centrifugation without any anti‑coagulants. Culture of MC3T3‑E1 cells with PRF induced the expression of osteoprotegerin (OPG), but had no effect on the expression of receptor activator of nuclear factor‑κB ligand (RANKL), increasing the OPG/RANKL ratio. Expression of other osteoblastic differentiation makers, including BMP‑2 and ‑4 and RUNX2, was not affected. PRF filling of a hole defect in the mental foramen bone of rats increased OPG positivity and decreased tartrate‑resistant acid phosphatase positivity compared with unfilled control. In conclusion, PRF increased the OPG/RANKL ratio by inducing OPG expression, suggesting that PRF enhances early stage osteogenesis by optimizing osteoblastic differentiation. The present study provides a scientific basis for clinical findings showing that PRF can enhance bone regeneration such as sinus lift.

View Figures

View References

1	Dohan DM, Choukroun J, Diss A, Dohan SL, Dohan AJ, Mouhyi J and Gogly B: Platelet-rich fibrin (PRF): A second-generation platelet concentrate. Part II: Platelet-related biologic features. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 101:e45–e50. 2006. View Article : Google Scholar : PubMed/NCBI
2	Senzel L, Gnatenko DV and Bahou WF: The platelet proteome. Curr Opin Hematol. 16:329–333. 2009. View Article : Google Scholar : PubMed/NCBI
3	Whitman DH, Berry RL and Green DM: Platelet gel: An autologous alternative to fibrin glue with applications in oral and maxillofacial surgery. J Oral Maxillofac Surg. 55:1294–1299. 1997. View Article : Google Scholar : PubMed/NCBI
4	Vaishnavi C, Mohan B and Narayanan LL: Treatment of endodontically induced periapical lesions using hydroxyapatite, platelet-rich plasma, and a combination of both: An in vivo study. J Conserv Dent. 14:140–146. 2011. View Article : Google Scholar : PubMed/NCBI
5	Gupta C, Mehrotra D, Mohammad S, Khanna V, Kumar Singh G, Singh G, Chellappa AA and Passi D: Alveolar bone graft with platelet rich plasma in cleft alveolus. J Oral Biol Craniofac Res. 3:3–8. 2013. View Article : Google Scholar : PubMed/NCBI
6	Kawase T: Platelet-rich plasma and its derivatives as promising bioactive materials for regenerative medicine: Basic principles and concepts underlying recent advances. Odontology. 103:126–135. 2015. View Article : Google Scholar : PubMed/NCBI
7	Dohan DM, Choukroun J, Diss A, Dohan SL, Dohan AJ, Mouhyi J and Gogly B: Platelet-rich fibrin (PRF): A second-generation platelet concentrate. Part I: Technological concepts and evolution. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 101:e37–e44. 2006. View Article : Google Scholar : PubMed/NCBI
8	Rodella LF, Favero G, Boninsegna R, Buffoli B, Labanca M, Scari G, Sacco L, Batani T and Rezzani R: Growth factors, CD34 positive cells, and fibrin network analysis in concentrated growth factors fraction. Microsc Res Tech. 74:772–777. 2011. View Article : Google Scholar : PubMed/NCBI
9	Durmuşlar MC, Balli U, Dede FÖ, Misir AF, Bariş E, Kürkçü M and Kahraman SA: Histological evaluation of the effect of concentrated growth factor on bone healing. J Craniofac Surg. 27:1494–1497. 2016. View Article : Google Scholar : PubMed/NCBI
10	Su CY, Kuo YP, Tseng YH, Su CH and Burnouf T: In vitro release of growth factors from platelet-rich fibrin (PRF): A proposal to optimize the clinical applications of PRF. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 108:56–61. 2009. View Article : Google Scholar : PubMed/NCBI
11	Raggatt LJ and Partridge NC: Cellular and molecular mechanisms of bone remodeling. J Biol Chem. 285:25103–25108. 2010. View Article : Google Scholar : PubMed/NCBI
12	Franceschi RT and Iyer BS: Relationship between collagen synthesis and expression of the osteoblast phenotype in MC3T3-E1 cells. J Bone Miner Res. 7:235–246. 1992. View Article : Google Scholar : PubMed/NCBI
13	Spelsberg TC, Subramaniam M, Riggs BL and Khosla S: The actions and interactions of sex steroids and growth factors/cytokines on the skeleton. Mol Endocrinol. 13:819–828. 1999. View Article : Google Scholar : PubMed/NCBI
14	Maeda T, Matsunuma A, Kawane T and Horiuchi N: Simvastatin promotes osteoblast differentiation and mineralization in MC3T3-E1 cells. Biochem Biophys Res Commun. 280:874–877. 2001. View Article : Google Scholar : PubMed/NCBI
15	Wu M, Chen G and Li YP: TGF-β and BMP signaling in osteoblast, skeletal development, and bone formation, homeostasis and disease. Bone Res. 4:160092016. View Article : Google Scholar : PubMed/NCBI
16	Sparks AB, Morin PJ, Vogelstein B and Kinzler KW: Mutational analysis of the APC/beta-catenin/Tcf pathway in colorectal cancer. Cancer Res. 58:1130–1134. 1998.PubMed/NCBI
17	Dejmek J, Säfholm A, Kamp Nielsen C, Andersson T and Leandersson K: Wnt-5a/Ca²⁺-induced NFAT activity is counteracted by Wnt-5a/Yes-Cdc42-casein kinase 1alpha signaling in human mammary epithelial cells. Mol Cell Biol. 26:6024–6036. 2006. View Article : Google Scholar : PubMed/NCBI
18	Lin SS, Ueng SW, Niu CC, Yuan LJ, Yang CY, Chen WJ, Lee MS and Chen JK: Hyperbaric oxygen promotes osteogenic differentiation of bone marrow stromal cells by regulating Wnt3a/β-catenin signaling-an in vitro and in vivo study. Stem Cell Res. 12:260–274. 2014. View Article : Google Scholar : PubMed/NCBI
19	Krause U, Harris S, Green A, Ylostalo J, Zeitouni S, Lee N and Gregory CA: Pharmaceutical modulation of canonical Wnt signaling in multipotent stromal cells for improved osteoinductive therapy. Proc Natl Acad Sci USA. 107:4147–4152. 2010. View Article : Google Scholar : PubMed/NCBI
20	Anderson DM, Maraskovsky E, Billingsley WL, Dougall WC, Tometsko ME, Roux ER, Teepe MC, DuBose RF, Cosman D and Galibert L: A homologue of the TNF receptor and its ligand enhance T-cell growth and dendritic-cell function. Nature. 390:175–179. 1997. View Article : Google Scholar : PubMed/NCBI
21	Sato MM, Nakashima A, Nashimoto M, Yawaka Y and Tamura M: Bone morphogenetic protein-2 enhances Wnt/beta-catenin signaling-induced osteoprotegerin expression. Genes Cells. 14:141–153. 2009. View Article : Google Scholar : PubMed/NCBI
22	Chang IC, Tsai CH and Chang YC: Platelet-rich fibrin modulates the expression of extracellular signal-regulated protein kinase and osteoprotegerin in human osteoblasts. J Biomed Mater Res A. 95:327–332. 2010. View Article : Google Scholar : PubMed/NCBI
23	Rogers A, Saleh G, Hannon RA, Greenfield D and Eastell R: Circulating estradiol and osteoprotegerin as determinants of bone turnover and bone density in postmenopausal women. J Clin Endocrinol Metab. 87:4470–4475. 2002. View Article : Google Scholar : PubMed/NCBI
24	Maeda T, Suzuki A, Yuzawa S, Baba Y, Kimura Y and Kato Y: Mineral trioxide aggregate induces osteoblastogenesis via Atf6. Bone Rep. 2:36–43. 2015. View Article : Google Scholar : PubMed/NCBI
25	Kim TH, Kim SH, Sándor GK and Kim YD: Comparison of platelet-rich plasma (PRP), platelet-rich fibrin (PRF), and concentrated growth factor (CGF) in rabbit-skull defect healing. Arch Oral Biol. 59:550–558. 2014. View Article : Google Scholar : PubMed/NCBI
26	Fukui N, Ueno T, Ito Y, Takahashi Y, Kimura Y, Nakajima Y, Kasuya S, Kanou M, Takubo K, Yamamoto K, et al: Quantification of growth factors in platelet-rich Fibrin: A preliminary study. J Hard Tissue Biol. 24:231–234. 2015. View Article : Google Scholar
27	Ogino Y, Ayukawa Y, Kukita T, Atsuta I and Koyano K: Platelet-rich plasma suppresses osteoclastogenesis by promoting the secretion of osteoprotegerin. J Periodontal Res. 44:217–224. 2009. View Article : Google Scholar : PubMed/NCBI
28	Khadra M, Kasem N, Haanaes HR, Ellingsen JE and Lyngstadaas SP: Enhancement of bone formation in rat calvarial bone defects using low-level laser therapy. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 97:693–700. 2004. View Article : Google Scholar : PubMed/NCBI
29	Choukroun J, Diss A, Simonpieri A, Girard MO, Schoeffler C, Dohan SL, Dohan AJ, Mouhyi J and Dohan DM: Platelet-rich fibrin (PRF): A second-generation platelet concentrate. Part IV: Clinical effects on tissue healing. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 101:e56–e60. 2006. View Article : Google Scholar : PubMed/NCBI
30	Pripatnanont P, Nuntanaranont T, Vongvatcharanon S and Phurisat K: The primacy of platelet-rich fibrin on bone regeneration of various grafts in rabbit's calvarial defects. J Craniomaxillofac Surg. 41:e191–e200. 2013. View Article : Google Scholar : PubMed/NCBI
31	Yamazaki T, Tetsuya K and Yokose S: Histological demonstration of bone healing in rat tibiae influenced by diode laser irradiation. J Japan Soc Laser Surg Med. 37:80–86. 2016.
32	Simonet WS, Lacey DL, Dunstan CR, Kelley M, Chang MS, Lüthy R, Nguyen HQ, Wooden S, Bennett L, Boone T, et al: Osteoprotegerin: A novel secreted protein involved in the regulation of bone density. Cell. 89:309–319. 1997. View Article : Google Scholar : PubMed/NCBI
33	Yasuda H, Shima N, Nakagawa N, Yamaguchi K, Kinosaki M, Mochizuki S, Tomoyasu A, Yano K, Goto M, Murakami A, et al: Osteoclast differentiation factor is a ligand for osteoprotegerin/osteoclastogenesis-inhibitory factor and is identical to TRANCE/RANKL. Proc Natl Acad Sci USA. 95:3597–3602. 1998. View Article : Google Scholar : PubMed/NCBI
34	Yang X, Wang Y, Han X, Shu R, Chen T, Zeng H, Xu X, Huang L, Ren A, Song J, et al: Effects of TGF-β1 on OPG/RANKL expression of cementoblasts and osteoblasts are similar without stress but different with mechanical compressive stress. Scientific World Journal. 2015:7181802015. View Article : Google Scholar : PubMed/NCBI
35	Baek KJ, Choi Y and Ji S: Gingival fibroblasts from periodontitis patients exhibit inflammatory characteristics in vitro. Arch Oral Biol. 58:1282–1292. 2013. View Article : Google Scholar : PubMed/NCBI
36	Gautam J, Khedgikar V, Choudhary D, Kushwaha P, Dixit P, Singh D, Maurya R and Trivedi R: An isoflavone cladrin prevents high-fat diet-induced bone loss and inhibits the expression of adipogenic gene regulators in 3T3-L1 adipocyte. J Pharm Pharmacol. 68:1051–1063. 2016. View Article : Google Scholar : PubMed/NCBI
37	Songia P, Branchetti E, Parolari A, Myasoedova V, Ferrari G, Alamanni F, Tremoli E and Poggio P: Mitral valve endothelial cells secrete osteoprotegerin during endothelial mesenchymal transition. J Mol Cell Cardiol. 98:48–57. 2016. View Article : Google Scholar : PubMed/NCBI
38	Sahni A and Francis CW: Vascular endothelial growth factor binds to fibrinogen and fibrin and stimulates endothelial cell proliferation. Blood. 96:3772–3778. 2000.PubMed/NCBI
39	van Hinsbergh VW, Collen A and Koolwijk P: Role of fibrin matrix in angiogenesis. Ann NY Acad Sci. 936:426–437. 2001. View Article : Google Scholar : PubMed/NCBI
40	Tajima N, Ohba S, Sawase T and Asahina I: Evaluation of sinus floor augmentation with simultaneous implant placement using platelet-rich fibrin as sole grafting material. Int J Oral Maxillofac Implants. 28:77–83. 2013. View Article : Google Scholar : PubMed/NCBI
41	Choukroun J, Diss A, Simonpieri A, Girard MO, Schoeffler C, Dohan SL, Dohan AJ, Mouhyi J and Dohan DM: Platelet-rich fibrin (PRF): A second-generation platelet concentrate. Part V: Histologic evaluations of PRF effects on bone allograft maturation in sinus lift. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 101:299–303. 2006. View Article : Google Scholar : PubMed/NCBI
42	Takeda Y, Katsutoshi K, Matsuzaka K and Inoue T: The effect of concentrated growth factor on rat bone marrow cells in vitro and on calvarial bone healing in vivo. Int J Oral Maxillofac Implants. 30:1187–1196. 2015. View Article : Google Scholar : PubMed/NCBI
43	Litvinov RI and Weisel JW: What is the biological and clinical relevance of fibrin? Semin Thromb Hemost. 42:333–343. 2016. View Article : Google Scholar : PubMed/NCBI
44	Marx RE, Carlson ER, Eichstaedt RM, Schimmele SR, Strauss JE and Georgeff KR: Platelet-rich plasma: Growth factor enhancement for bone grafts. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 85:638–646. 1998. View Article : Google Scholar : PubMed/NCBI
45	Plachokova AS, Nikolidakis D, Mulder J, Jansen JA and Creugers NH: Effect of platelet-rich plasma on bone regeneration in dentistry: A systematic review. Clin Oral Implants Res. 19:539–545. 2008. View Article : Google Scholar : PubMed/NCBI
46	Roffi A, Di Matteo B, Krishnakumar GS, Kon E and Filardo G: Platelet-rich plasma for the treatment of bone defects: From pre-clinical rational to evidence in the clinical practice. A systematic review. Int Orthop. 41:221–237. 2017. View Article : Google Scholar : PubMed/NCBI
47	Broggini N, Hofstetter W, Hunziker E, Bosshardt DD, Bornstein MM, Seto I, Weibrich G and Buser D: The influence of PRP on early bone formation in membrane protected defects. A histological and histomorphometric study in the rabbit calvaria. Clin Implant Dent Relat Res. 13:1–12. 2011. View Article : Google Scholar : PubMed/NCBI
48	Simonpieri A, Del Corso M, Vervelle A, Jimbo R, Inchingolo F, Sammartino G and Dohan Ehrenfest DM: Current knowledge and perspectives for the use of platelet-rich plasma (PRP) and platelet-rich fibrin (PRF) in oral and maxillofacial surgery part 2: Bone graft, implant and reconstructive surgery. Curr Pharm Biotechnol. 13:1231–1256. 2012. View Article : Google Scholar : PubMed/NCBI
49	Quarles LD, Yohay DA, Lever LW, Caton R and Wenstrup RJ: Distinct proliferative and differentiated stages of murine MC3T3-E1 cells in culture: An in vitro model of osteoblast development. J Bone Miner Res. 7:683–692. 1992. View Article : Google Scholar : PubMed/NCBI
50	Li F, Yang Y, Zhu P, Chen W, Qi D, Shi X, Zhang C, Yang Z and Li P: Echinacoside promotes bone regeneration by increasing OPG/RANKL ratio in MC3T3-E1 cells. Fitoterapia. 83:1443–1450. 2012. View Article : Google Scholar : PubMed/NCBI
51	Chen X, Garner SC, Quarles LD and Anderson JJ: Effects of genistein on expression of bone markers during MC3T3-E1 osteoblastic cell differentiation. J Nutr Biochem. 14:342–349. 2003. View Article : Google Scholar : PubMed/NCBI
52	Gori F, Hofbauer LC, Dunstan CR, Spelsberg TC, Khosla S and Riggs BL: The expression of osteoprotegerin and RANK ligand and the support of osteoclast formation by stromal-osteoblast lineage cells is developmentally regulated. Endocrinology. 141:4768–4776. 2000. View Article : Google Scholar : PubMed/NCBI
53	Clark RA: Fibrin and wound healing. Ann NY Acad Sci. 936:355–367. 2001. View Article : Google Scholar : PubMed/NCBI
54	Intini G: The use of platelet-rich plasma in bone reconstruction therapy. Biomaterials. 30:4956–4966. 2009. View Article : Google Scholar : PubMed/NCBI
55	Anitua E, Andia I, Ardanza B, Nurden P and Nurden AT: Autologous platelets as a source of proteins for healing and tissue regeneration. Thromb Haemost. 91:4–15. 2004. View Article : Google Scholar : PubMed/NCBI
56	Marques LF, Stessuk T, Camargo IC, Sabeh Junior N, dos Santos L and Ribeiro-Paes JT: Platelet-rich plasma (PRP): Methodological aspects and clinical applications. Platelets. 26:101–113. 2015. View Article : Google Scholar : PubMed/NCBI
57	Silva I and Branco JC: Rank/Rankl/opg: Literature review. Acta Reumatol Port. 36:209–218. 2011.PubMed/NCBI
58	McCarthy HS, Williams JH, Davie MW and Marshall MJ: Platelet-derived growth factor stimulates osteoprotegerin production in osteoblastic cells. J Cell Physiol. 218:350–354. 2009. View Article : Google Scholar : PubMed/NCBI
59	Ikebuchi Y, Aoki S, Honma M, Hayashi M, Sugamori Y, Khan M, Kariya Y, Kato G, Tabata Y, Penninger JM, et al: Coupling of bone resorption and formation by RANKL reverse signalling. Nature. 561:195–200. 2018. View Article : Google Scholar : PubMed/NCBI
60	Fei Q, Guo C, Xu X, Gao J, Zhang J, Chen T and Cui D: Osteogenic growth peptide enhances the proliferation of bone marrow mesenchymal stem cells from osteoprotegerin-deficient mice by CDK2/cyclin A. Acta Biochim Biophys Sin (Shanghai). 42:801–806. 2010. View Article : Google Scholar : PubMed/NCBI
61	Kapse S, Surana S, Satish M, Hussain SE, Vyas S and Thakur D: Autologous platelet-rich fibrin: Can it secure a better healing? Oral Surg Oral Med Oral Pathol Oral Radiol. 127:8–18. 2019. View Article : Google Scholar : PubMed/NCBI