Platelet concentrates for bone regeneration: Current evidence and future challenges

References

• AlGhamdi AS, Shibly O, Ciancio SG. Osseous grafting part II: Xenografts and alloplasts for periodontal regeneration–a literature review. J Int Acad Periodontol 2010;12:39–44.
   PubMedGoogle Scholar
• AlGhamdi AS, Shibly O, Ciancio SG. Osseous grafting part I: Autografts and allografts for periodontal regeneration–a literature review. J Int Acad Periodontol 2010;12:34–38.
   PubMedGoogle Scholar
• Carlson ER. Bone grafting the jaws in the 21st century: The use of platelet-rich plasma and bone morphogenetic protein. Alpha Omegan 2000;93:26–30. Epub 2001/02/24.
   PubMedGoogle Scholar
• Marx RE, Carlson ER, Eichstaedt RM, Schimmele SR, Strauss JE, Georgeff KR. Platelet-rich plasma: Growth factor enhancement for bone grafts. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 1998;85:638–646.
   PubMed Web of Science ®Google Scholar
• Intini G. The use of platelet-rich plasma in bone reconstruction therapy. Biomaterials 2009;30:4956–4966. Epub 2009/07/04.
   PubMed Web of Science ®Google Scholar
• Alsousou J, Ali A, Willett K, Harrison P. The role of platelet-rich plasma in tissue regeneration. Platelets 2013;24:173–182. Epub 2012/06/01.
   PubMed Web of Science ®Google Scholar
• Taylor DW, Petrera M, Hendry M, Theodoropoulos JS. A systematic review of the use of platelet-rich plasma in sports medicine as a new treatment for tendon and ligament injuries. Clin J Sport Med 2011;21:344–352.
   PubMed Web of Science ®Google Scholar
• Moraschini V, Barboza ES. Effect of autologous platelet concentrates for alveolar socket preservation: A systematic review. Int J Oral Maxillofac Surg 2015;44:632–641. Epub 2015/01/30.
   PubMed Web of Science ®Google Scholar
• Torres J, Tamimi F, Alkhraisat MH, Manchon A, Linares R, Prados-Frutos JC, Hernandez G, Lopez Cabarcos E. Platelet-rich plasma may prevent titanium-mesh exposure in alveolar ridge augmentation with anorganic bovine bone. J Clin Periodontol 2010;37:943–951.
   PubMed Web of Science ®Google Scholar
• Drago L, Bortolin M, Vassena C, Taschieri S, Del Fabbro M. Antimicrobial activity of pure platelet-rich plasma against microorganisms isolated from oral cavity. BMC Microbiol 2013;13:47.
   PubMed Web of Science ®Google Scholar
• Navani A, Li G, Chrystal J. Platelet rich plasma in musculoskeletal pathology: A necessary rescue or a lost cause? Pain Physician 2017;20:E345–E56.
   PubMed Web of Science ®Google Scholar
• Al-Hamed FS, Tawfik MA, Abdelfadil E, Al-Saleh MA. Efficacy of platelet-rich fibrin after mandibular third molar extraction: A systematic review and meta-analysis. J Oral Maxillofac Surg 2017;75:1124–1135.
   PubMed Web of Science ®Google Scholar
• Masuki H, Okudera T, Watanebe T, Suzuki M, Nishiyama K, Okudera H, Nakata K, Uematsu K, Su CY, Kawase T. Growth factor and pro-inflammatory cytokine contents in platelet-rich plasma (PRP), plasma rich in growth factors (PRGF), advanced platelet-rich fibrin (A-PRF), and concentrated growth factors (CGF). Int J Implant Dent 2016;2:19.
   PubMed Web of Science ®Google Scholar
• Schmidt-Bleek K, Willie BM, Schwabe P, Seemann P, Duda GN. BMPs in bone regeneration: Less is more effective, a paradigm-shift. Cytokine Growth Factor Rev 2016;27:141–148.
   PubMed Web of Science ®Google Scholar
• Swiontkowski MF, Aro HT, Donell S, Esterhai JL, Goulet J, Jones A, Kregor PJ, Nordsletten L, Paiement G, Patel A. Recombinant human bone morphogenetic protein-2 in open tibial fractures. A subgroup analysis of data combined from two prospective randomized studies. J Bone Joint Surg Am 2006;88:1258–1265.
   PubMed Web of Science ®Google Scholar
• Jung RE, Glauser R, Scharer P, Hammerle CH, Sailer HF, Weber FE. Effect of rhBMP-2 on guided bone regeneration in humans. Clin Oral Implants Res 2003;14:556–568.
   PubMed Web of Science ®Google Scholar
• Dohan Ehrenfest DM, Rasmusson L, Albrektsson T. Classification of platelet concentrates: from pure platelet-rich plasma (P-PRP) to leucocyte- and platelet-rich fibrin (L-PRF). Trends Biotechnol 2009;27:158–167.
   PubMed Web of Science ®Google Scholar
• Borie E, Olivi DG, Orsi IA, Garlet K, Weber B, Beltran V, Fuentes R. Platelet-rich fibrin application in dentistry: A literature review. Int J Clin Exp Med 2015;8:7922–7929. Epub 2015/07/30.
   PubMed Web of Science ®Google Scholar
• Weibrich G, Hansen T, Kleis W, Buch R, Hitzler WE. Effect of platelet concentration in platelet-rich plasma on peri-implant bone regeneration. Bone 2004;34:665–671. Epub 2004/03/31.
   PubMed Web of Science ®Google Scholar
• Marx RE. Platelet-rich plasma (PRP): what is PRP and what is not PRP? Implant Dent 2001;10:225–228.
   PubMedGoogle Scholar
• Choi BH, Zhu SJ, Kim BY, Huh JY, Lee SH, Jung JH. Effect of platelet-rich plasma (PRP) concentration on the viability and proliferation of alveolar bone cells: an in vitro study. Int J Oral Maxillofac Surg 2005;34:420–424.
   PubMed Web of Science ®Google Scholar
• Dhurat R, Sukesh M. Principles and methods of preparation of platelet-rich plasma: A review and author’s perspective. J Cutan Aesthet Surg 2014;7:189–197.
   PubMedGoogle Scholar
• Malhotra R, Kumar V, Garg B, Singh R, Jain V, Coshic P, Chatterjee K. Role of autologous platelet-rich plasma in treatment of long-bone nonunions: a prospective study. Musculoskelet Surg 2015;99:243–248. Epub 2015/07/22.
   PubMedGoogle Scholar
• Malhotra A, Pelletier MH, Yu Y, Walsh WR. Can platelet-rich plasma (PRP) improve bone healing? A comparison between the theory and experimental outcomes. Arch Orthop Trauma Surg 2013;133:153–165. Epub 2012/12/01.
   PubMed Web of Science ®Google Scholar
• Cmolik BL, Spero JA, Magovern GJ, Clark RE. Redo cardiac surgery: late bleeding complications from topical thrombin-induced factor V deficiency. J Thorac Cardiovasc Surg 1993;105:222–227. discussion 7-8.
   PubMed Web of Science ®Google Scholar
• Cavallo C, Roffi A, Grigolo B, Mariani E, Pratelli L, Merli G, Kon E, Marcacci M, Filardo G. Platelet-rich plasma: The choice of activation method affects the release of bioactive molecules. Biomed Res Int 2016;2016:6591717.
   PubMed Web of Science ®Google Scholar
• Jonnalagadda D, Izu LT, Whiteheart SW. Platelet secretion is kinetically heterogeneous in an agonist-responsive manner. Blood 2012;120:5209–5216.
   PubMed Web of Science ®Google Scholar
• Kumar RV, Shubhashini N. Platelet rich fibrin: a new paradigm in periodontal regeneration. Cell Tissue Bank 2013;14:453–463. Epub 2012/11/13.
   PubMed Web of Science ®Google Scholar
• Gassling V, Douglas T, Warnke PH, Acil Y, Wiltfang J, Becker ST. Platelet-rich fibrin membranes as scaffolds for periosteal tissue engineering. Clin Oral Implants Res 2010;21:543–549.
   PubMed Web of Science ®Google Scholar
• Wen Y, Gu W, Cui J, Yu M, Zhang Y, Tang C, Yang P, Xu X. Platelet-rich plasma enhanced umbilical cord mesenchymal stem cells-based bone tissue regeneration. Arch Oral Biol 2014;59:1146–1154. Epub 2014/08/05.
   PubMed Web of Science ®Google Scholar
• Chang YC, Zhao JH. Effects of platelet-rich fibrin on human periodontal ligament fibroblasts and application for periodontal infrabony defects. Aust Dent J 2011;56:365–371. Epub 2011/12/01.
   PubMed Web of Science ®Google Scholar
• Clipet F, Tricot S, Alno N, Massot M, Solhi H, Cathelineau G, Perez F, De Mello G, Pellen-Mussi P. In vitro effects of Choukroun’s platelet-rich fibrin conditioned medium on 3 different cell lines implicated in dental implantology. Implant Dent 2012;21:51–56. Epub 2011/10/12.
   PubMed Web of Science ®Google Scholar
• Cvetkovic VJ, Najdanovic JG, Vukelic-Nikolic MD, Stojanovic S, Najman SJ. Osteogenic potential of in vitro osteo-induced adipose-derived mesenchymal stem cells combined with platelet-rich plasma in an ectopic model. Int Orthop 2015;39:2173–2180. Epub 2015/08/02.
   PubMed Web of Science ®Google Scholar
• Lin SS, Landesberg R, Chin HS, Lin J, Eisig SB, Lu HH. Controlled release of PRP-derived growth factors promotes osteogenic differentiation of human mesenchymal stem cells. Conf Proc IEEE Eng Med Biol Soc 2006;1:4358–4361. Epub 2007/10/20.
   PubMedGoogle Scholar
• Parsons P, Butcher A, Hesselden K, Ellis K, Maughan J, Milner R, Scott M, Alley C, Watson JT, Horner A. Platelet-rich concentrate supports human mesenchymal stem cell proliferation, bone morphogenetic protein-2 messenger RNA expression, alkaline phosphatase activity, and bone formation in vitro: A mode of action to enhance bone repair. J Orthop Trauma 2008;22:595–604. Epub 2008/10/02.
   PubMed Web of Science ®Google Scholar
• Arpornmaeklong P, Kochel M, Depprich R, Kubler NR, Wurzler KK. Influence of platelet-rich plasma (PRP) on osteogenic differentiation of rat bone marrow stromal cells. An in vitro study. Int J Oral Maxillofac Surg 2004;33:60–70.
   PubMed Web of Science ®Google Scholar
• Soffer E, Ouhayoun JP, Dosquet C, Meunier A, Anagnostou F. Effects of platelet lysates on select bone cell functions. Clin Oral Implants Res 2004;15:581–588.
   PubMed Web of Science ®Google Scholar
• Roffi A, Di Matteo B, Krishnakumar GS, Kon E, 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 2017;41:221–237.
   PubMed Web of Science ®Google Scholar
• Kon E, Filardo G, Delcogliano M, Fini M, Salamanna F, Giavaresi G, Martin I, Marcacci M. Platelet autologous growth factors decrease the osteochondral regeneration capability of a collagen-hydroxyapatite scaffold in a sheep model. BMC Musculoskelet Disord 2010;11:220. Epub 2010/09/30.
   PubMed Web of Science ®Google Scholar
• Torres J, Tamimi F, Tresguerres IF, Alkhraisat MH, Khraisat A, Blanco L, Lopez-Cabarcos E. Effect of combining platelet-rich plasma with anorganic bovine bone on vertical bone regeneration: Early healing assessment in rabbit calvariae. Int J Oral Maxillofac Implants 2010;25:123–129.
   PubMed Web of Science ®Google Scholar
• Torres J, Tamimi FM, Tresguerres IF, Alkhraisat MH, Khraisat A, Lopez-Cabarcos E, Blanco L. Effect of solely applied platelet-rich plasma on osseous regeneration compared to Bio-Oss: A morphometric and densitometric study on rabbit calvaria. Clin Implant Dent Relat Res 2008;10:106–112.
   PubMed Web of Science ®Google Scholar
• Schroeder CC, Scariot JS, Ribeiro JC, Deliberador TM, Giovanini AM. Platelet rich plasma (PRP) produces an atherofibrotic histophenotype during craniofacial bone repair due to changes of immunohistochemical expression of Erk1/2, p38alpha/beta, adiponectin and elevated presence of cells exhibiting B-scavenger receptor (CD36+). Braz Dent J 2016;27:243–254. Epub 2016/05/26.
   PubMedGoogle Scholar
• Cerci DX, Portela GS, Cunha EJ, Grossi JR, Zielak JC, Araujo MR, Scariot R, Deliberador TM, Giovanini AF. Leukocyte-platelet-rich plasma diminishes bone matrix deposition in rat calvaria treated with autograft due to simultaneous increase in immunohistochemical expression of Indian Hedgehog, transforming growth factor-beta, and parathyroid-1 receptor. J Craniomaxillofac Surg 2015;43:1470–1477. Epub 2015/07/30.
   PubMed Web of Science ®Google Scholar
• Giovanini AF, Grossi JR, Gonzaga CC, Zielak JC, Gohringer I, Vieira Jde S, Kuczera J, De Oliveira Filho MA, Deliberador TM. Leukocyte-platelet-rich plasma (L-PRP) induces an abnormal histophenotype in craniofacial bone repair associated with changes in the immunopositivity of the hematopoietic clusters of differentiation, osteoproteins, and TGF-beta1. Clin Implant Dent Relat Res 2014;16:259–272. Epub 2012/07/19.
   PubMed Web of Science ®Google Scholar
• Hao PJ, Wang ZG, Xu QC, Xu S, Li ZR, Yang PS, Liu ZH. Effect of umbilical cord mesenchymal stem cell in peri-implant bone defect after immediate implant: an experiment study in beagle dogs. Int J Clin Exp Pathol 2014;7:8271–8278. Epub 2015/01/01.
   PubMed Web of Science ®Google Scholar
• Suaid FF, Carvalho MD, Ambrosano GM, Nociti FH Jr., Casati MZ, Sallum EA. Platelet-rich plasma in the treatment of Class II furcation defects: A histometrical study in dogs. J Appl Oral Sci 2012;20:162–169. Epub 2012/06/06.
   PubMed Web of Science ®Google Scholar
• Yilmaz D, Dogan N, Ozkan A, Sencimen M, Ora BE, Mutlu I. Effect of platelet rich fibrin and beta tricalcium phosphate on bone healing. A histological study in pigs. Acta Cir Bras 2014;29:59–65. Epub 2014/01/30.
   PubMed Web of Science ®Google Scholar
• Del Corso M, Vervelle A, Simonpieri A, Jimbo R, Inchingolo F, Sammartino G, 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 1: periodontal and dentoalveolar surgery. Curr Pharm Biotechnol 2012;13:1207–1230. Epub 2011/07/12.
   PubMed Web of Science ®Google Scholar
• Simonpieri A, Del Corso M, Vervelle A, Jimbo R, Inchingolo F, Sammartino G, 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 2012;13:1231–1256. Epub 2011/07/12.
   PubMed Web of Science ®Google Scholar
• Torres J, Tamimi F, Martinez PP, Alkhraisat MH, Linares R, Hernandez G, Torres-Macho J, Lopez-Cabarcos E. Effect of platelet-rich plasma on sinus lifting: A randomized-controlled clinical trial. J Clin Periodontol 2009;36:677–687.
   PubMed Web of Science ®Google Scholar
• Celio-Mariano R, De Melo WM, Carneiro-Avelino C. Comparative radiographic evaluation of alveolar bone healing associated with autologous platelet-rich plasma after impacted mandibular third molar surgery. J Oral Maxillofac Surg 2012;70:19–24. Epub 2011/07/23.
   PubMed Web of Science ®Google Scholar
• Kumar N, Prasad K, Ramanujam LKR, Dexith J, Chauhan A. Evaluation of treatment outcome after impacted mandibular third molar surgery with the use of autologous platelet-rich fibrin: A randomized controlled clinical study. J Oral Maxillofac Surg 2015;73:1042–1049. Epub 2015/02/11.
   PubMed Web of Science ®Google Scholar
• Simon D, Manuel S, Geetha V, Naik BR. Potential for osseous regeneration of platelet-rich plasma–a comparative study in mandibular third molar sockets. Indian J Dent Res 2004;15:133–136. Epub 2005/07/23.
   PubMedGoogle Scholar
• Dori F, Huszar T, Nikolidakis D, Tihanyi D, Horvath A, Arweiler NB, Gera I, Sculean A. Effect of platelet-rich plasma on the healing of intrabony defects treated with Beta tricalcium phosphate and expanded polytetrafluoroethylene membranes. J Periodontol 2008;79:660–669. Epub 2008/04/03.
   PubMed Web of Science ®Google Scholar
• Menezes LM, Rao J. Long-term clinical evaluation of platelet-rich plasma in the treatment of human periodontal intraosseous defects: A comparative clinical trial. Quintessence Int 2012;43:571–582. Epub 2012/06/07.
   PubMed Web of Science ®Google Scholar
• Arora NS, Ramanayake T, Ren YF, Romanos GE. Platelet-rich plasma in sinus augmentation procedures: A systematic literature review: Part II. Implant Dent 2010;19:145–157. Epub 2010/04/14.
   PubMed Web of Science ®Google Scholar
• Plachokova AS, Nikolidakis D, Mulder J, Jansen JA, Creugers NH. Effect of platelet-rich plasma on bone regeneration in dentistry: A systematic review. Clin Oral Implants Res 2008;19:539–545. Epub 2008/04/22.
   PubMed Web of Science ®Google Scholar
• Roffi A, Filardo G, Kon E, Marcacci M. Does PRP enhance bone integration with grafts, graft substitutes, or implants? A systematic review. BMC Musculoskelet Disord 2013;14:330. Epub 2013/11/23.
   PubMed Web of Science ®Google Scholar
• Del Fabbro M, Bortolin M, Taschieri S, Weinstein R. Is platelet concentrate advantageous for the surgical treatment of periodontal diseases? A systematic review and meta-analysis. J Periodontol 2011;82:1100–1111. Epub 2010/12/30.
   PubMed Web of Science ®Google Scholar
• Del Fabbro M, Bortolin M, Taschieri S, Weinstein RL. Effect of autologous growth factors in maxillary sinus augmentation: A systematic review. Clin Implant Dent Relat Res 2013;15:205–216.
   PubMed Web of Science ®Google Scholar
• Pocaterra A, Caruso S, Bernardi S, Scagnoli L, Continenza MA, Gatto R. Effectiveness of platelet-rich plasma as an adjunctive material to bone graft: a systematic review and meta-analysis of randomized controlled clinical trials. Int J Oral Maxillofac Surg 2016;45:1027–1034.
   PubMed Web of Science ®Google Scholar
• Oncu E, Bayram B, Kantarci A, Gulsever S, Alaaddinoglu EE. Positive effect of platelet rich fibrin on osseointegration. Med Oral Patol Oral Cir Bucal 2016;21:e601–7. Epub 2016/08/01.
   PubMed Web of Science ®Google Scholar
• Singh A, Kohli M, Gupta N. Platelet rich fibrin: A novel approach for osseous regeneration. J Maxillofac Oral Surg 2012;11:430–434. Epub 2013/12/03.
   PubMedGoogle Scholar
• Castro AB, Meschi N, Temmerman A, Pinto N, Lambrechts P, Teughels W, Quirynen M. Regenerative potential of leucocyte- and platelet-rich fibrin. Part B: sinus floor elevation, alveolar ridge preservation and implant therapy. A systematic review. J Clin Periodontol 2017;44:225–234.
   PubMed Web of Science ®Google Scholar
• Panda S, Doraiswamy J, Malaiappan S, Varghese SS, Del Fabbro M. Additive effect of autologous platelet concentrates in treatment of intrabony defects: A systematic review and meta-analysis. J Investig Clin Dent 2016;7:13–26. Epub 2014/07/23.
   PubMed Web of Science ®Google Scholar
• Oryan A, Alidadi S, Moshiri A. Platelet-rich plasma for bone healing and regeneration. Expert Opin Biol Ther 2016;16:213–232. Epub 2015/11/13.
   PubMed Web of Science ®Google Scholar
• Del Fabbro M, Corbella S, Taschieri S, Francetti L, Weinstein R. Autologous platelet concentrate for post-extraction socket healing: A systematic review. Eur J Oral Implantol 2014;7:333–344. Epub 2014/11/26.
   PubMed Web of Science ®Google Scholar
• Tamimi FM, Montalvo S, Tresguerres I, Blanco Jerez L. A comparative study of 2 methods for obtaining platelet-rich plasma. J Oral Maxillofac Surg 2007;65:1084–1093.
   PubMed Web of Science ®Google Scholar
• Hamilton B, Tol JL, Knez W, Chalabi H. Exercise and the platelet activator calcium chloride both influence the growth factor content of platelet-rich plasma (PRP): Overlooked biochemical factors that could influence PRP treatment. Br J Sports Med 2015;49:957–960.
   PubMed Web of Science ®Google Scholar
• Roh YH, Kim W, Park KU, Oh JH. Cytokine-release kinetics of platelet-rich plasma according to various activation protocols. Bone Joint Res 2016;5:37–45.
   PubMed Web of Science ®Google Scholar
• Jeon YR, Jung BK, Roh TS, Kang EH, Lee WJ, Rah DK, Lew DH, Yun IS. Comparing the effect of nonactivated platelet-rich plasma, activated platelet-rich plasma, and bone morphogenetic Protein-2 on calvarial bone regeneration. J Craniofac Surg 2016;27:317–321.
   PubMed Web of Science ®Google Scholar
• Rendu F, Brohard-Bohn B. The platelet release reaction: Granules’ constituents, secretion and functions. Platelets 2001;12:261–273.
   PubMed Web of Science ®Google Scholar
• Zarpellon A, Donella-Deana A, Folda A, Turetta L, Pavanetto M, Deana R. Serotonin (5-HT) transport in human platelets is modulated by Src-catalysed Tyr-phosphorylation of the plasma membrane transporter SERT. Cell Physiol Biochem 2008;21:87–94.
   PubMed Web of Science ®Google Scholar
• De Vernejoul MC, Collet C, Chabbi-Achengli Y. Serotonin: Good or bad for bone. Bonekey Rep 2012;1:120.
   PubMedGoogle Scholar
• Westbroek I, Van Der Plas A, De Rooij KE, Klein-Nulend J, Nijweide PJ. Expression of serotonin receptors in bone. J Biol Chem 2001;276:28961–28968.
   PubMed Web of Science ®Google Scholar
• Nam SS, Lee JC, Kim HJ, Park JW, Lee JM, Suh JY, Um HS, Kim JY, Lee Y, Kim YG. Serotonin inhibits osteoblast differentiation and bone regeneration in rats. J Periodontol 2016;87:461–469.
   PubMed Web of Science ®Google Scholar
• Warden SJ, Robling AG, Haney EM, Turner CH, Bliziotes MM. The emerging role of serotonin (5-hydroxytryptamine) in the skeleton and its mediation of the skeletal effects of low-density lipoprotein receptor-related protein 5 (LRP5). Bone 2010;46:4–12.
   PubMed Web of Science ®Google Scholar
• Dai SQ, Yu LP, Shi X, Wu H, Shao P, Yin GY, Wei YZ. Serotonin regulates osteoblast proliferation and function in vitro. Braz J Med Biol Res 2014;47:759–765.
   PubMed Web of Science ®Google Scholar
• Yadav VK, Balaji S, Suresh PS, Liu XS, Lu X, Li Z, Guo XE, Mann JJ, Balapure AK, Gershon MD, Medhamurthy R, Vidal M, Karsenty G, Ducy P. Pharmacological inhibition of gut-derived serotonin synthesis is a potential bone anabolic treatment for osteoporosis. Nat Med 2010;16:308–312.
   PubMed Web of Science ®Google Scholar
• Tsapakis EM, Gamie Z, Tran GT, Adshead S, Lampard A, Mantalaris A, Tsiridis E. The adverse skeletal effects of selective serotonin reuptake inhibitors. Eur Psych 2012;27:156–169.
   Web of Science ®Google Scholar
• Wu X, Al-Abedalla K, Rastikerdar E, Abi Nader S, Daniel NG, Nicolau B, Tamimi F. Selective serotonin reuptake inhibitors and the risk of osseointegrated implant failure: a cohort study. J Dent Res 2014;93:1054–1061.
   PubMed Web of Science ®Google Scholar
• Gustafsson BI, Westbroek I, Waarsing JH, Waldum H, Solligard E, Brunsvik A, Dimmen S, Van Leeuwen JP, Weinans H, Syversen U. Long-term serotonin administration leads to higher bone mineral density, affects bone architecture, and leads to higher femoral bone stiffness in rats. J Cell Biochem 2006;97:1283–1291.
   PubMed Web of Science ®Google Scholar
• Mehta SK, Tucci MA, Benghuzzi HA. Effect of platelet dense granule contents upon osteoblast viability. Biomed Sci Instrum 2012;48:288–295.
   PubMedGoogle Scholar
• Cutarelli A, Marini M, Tancredi V, D’Arcangelo G, Murdocca M, Frank C, Tarantino U. Adenosine triphosphate stimulates differentiation and mineralization in human osteoblast-like Saos-2 cells. Dev Growth Differ 2016;58:400–408.
   PubMed Web of Science ®Google Scholar
• Hoebertz A, Mahendran S, Burnstock G, Arnett TR. ATP and UTP at low concentrations strongly inhibit bone formation by osteoblasts: A novel role for the P2Y(2) receptor in bone remodeling. J Cell Biochem 2002;86:413–419.
   PubMed Web of Science ®Google Scholar
• Orriss IR, Key ML, Hajjawi MO, Arnett TR. Extracellular ATP released by osteoblasts is a key local inhibitor of bone mineralisation. Plos One 2013;8:e69057.
   PubMed Web of Science ®Google Scholar
• Hoebertz A, Meghji S, Burnstock G, Arnett TR. Extracellular ADP is a powerful osteolytic agent: Evidence for signaling through the P2Y(1) receptor on bone cells. Faseb J 2001;15:1139–1148.
   PubMed Web of Science ®Google Scholar
• Jardin I, Lopez JJ, Pariente JA, Salido GM, Rosado JA. Intracellular calcium release from human platelets: Different messengers for multiple stores. Trends Cardiovasc Med 2008;18:57–61.
   PubMed Web of Science ®Google Scholar
• Dvorak MM, Riccardi D. Ca2+ as an extracellular signal in bone. Cell Calcium 2004;35:249–255.
   PubMed Web of Science ®Google Scholar
• Lorget F, Kamel S, Mentaverri R, Wattel A, Naassila M, Maamer M, Brazier M. High extracellular calcium concentrations directly stimulate osteoclast apoptosis. Biochem Biophys Res Commun 2000;268:899–903.
   PubMed Web of Science ®Google Scholar
• Ruiz FA, Lea CR, Oldfield E, Docampo R. Human platelet dense granules contain polyphosphate and are similar to acidocalcisomes of bacteria and unicellular eukaryotes. J Biol Chem 2004;279:44250–44257.
   PubMed Web of Science ®Google Scholar
• Francis MD. The inhibition of calcium hydroxypatite crystal growth by polyphosphonates and polyphosphates. Calcif Tissue Res 1969;3:151–162.
   PubMedGoogle Scholar
• Fleisch H, Schibler D, Maerki J, Frossard I. Inhibition of aortic calcification by means of pyrophosphate and polyphosphates. Nature 1965;207:1300–1301.
   PubMed Web of Science ®Google Scholar
• Hoac B, Kiffer-Moreira T, Millan JL, McKee MD. Polyphosphates inhibit extracellular matrix mineralization in MC3T3-E1 osteoblast cultures. Bone 2013;53:478–486.
   PubMed Web of Science ®Google Scholar
• Muller WE, Wang X, Diehl-Seifert B, Kropf K, Schlossmacher U, Lieberwirth I, Glasser G, Wiens M, Schroder HC. Inorganic polymeric phosphate/polyphosphate as an inducer of alkaline phosphatase and a modulator of intracellular Ca2+ level in osteoblasts (SaOS-2 cells) in vitro. Acta Biomater 2011;7:2661–2671.
   PubMed Web of Science ®Google Scholar
• Hacchou Y, Uematsu T, Ueda O, Usui Y, Uematsu S, Takahashi M, Uchihashi T, Kawazoe Y, Shiba T, Kurihara S, Yamaoka M, Furusawa K. Inorganic polyphosphate: a possible stimulant of bone formation. J Dent Res 2007;86:893–897.
   PubMed Web of Science ®Google Scholar
• Wu M, Chen G, Li YP. TGF-beta and BMP signaling in osteoblast, skeletal development, and bone formation, homeostasis and disease. Bone Res 2016;4:16009.
   PubMed Web of Science ®Google Scholar
• Ferrara N, Gerber HP. The role of vascular endothelial growth factor in angiogenesis. Acta Haematol 2001;106:148–156.
   PubMed Web of Science ®Google Scholar
• Gerber HP, Vu TH, Ryan AM, Kowalski J, Werb Z, Ferrara N. VEGF couples hypertrophic cartilage remodeling, ossification and angiogenesis during endochondral bone formation. Nat Med 1999;5:623–628.
   PubMed Web of Science ®Google Scholar
• Ornitz DM, Marie PJ. Fibroblast growth factor signaling in skeletal development and disease. Genes Dev 2015;29:1463–1486.
   PubMed Web of Science ®Google Scholar
• Zhou FH, Foster BK, Sander G, Xian CJ. Expression of proinflammatory cytokines and growth factors at the injured growth plate cartilage in young rats. Bone 2004;35:1307–1315.
   PubMed Web of Science ®Google Scholar
• Heldin CH, Westermark B. Mechanism of action and in vivo role of platelet-derived growth factor. Physiol Rev 1999;79:1283–1316.
   PubMed Web of Science ®Google Scholar
• Lee YM, Fujikado N, Manaka H, Yasuda H, Iwakura Y. IL-1 plays an important role in the bone metabolism under physiological conditions. Int Immunol 2010;22:805–816.
   PubMed Web of Science ®Google Scholar
• Franchimont N, Wertz S, Malaise M. Interleukin-6: An osteotropic factor influencing bone formation? Bone 2005;37:601–606.
   PubMed Web of Science ®Google Scholar
• Heijnen H, Van Der Sluijs P. Platelet secretory behaviour: As diverse as the granules … or not? J Thromb Haemost 2015;13:2141–2151.
   PubMed Web of Science ®Google Scholar
• Varon D, Shai E. Platelets and their microparticles as key players in pathophysiological responses. J Thromb Haemost 2015;13(Suppl 1):S40–6.
   PubMed Web of Science ®Google Scholar