769
Views
56
CrossRef citations to date
0
Altmetric
Review

A new strategy to tackle severe knee osteoarthritis: Combination of intra-articular and intraosseous injections of Platelet Rich Plasma

, , , , , , , & show all
Pages 627-643 | Received 18 Dec 2015, Accepted 18 Feb 2016, Published online: 21 Mar 2016

References

  • Little CB, Hunter DJ. Post-traumatic osteoarthritis: from mouse models to clinical trials. Nat Rev Rheumatol. 2013;9:485–497. doi:10.1038/nrrheum.2013.72.
  • De Lange-Brokaar B, Ioan-Facsinay A, Van Osch G, et al. Synovial inflammation, immune cells and their cytokines in osteoarthritis: a review. Osteoarthr Cartil. 2012;20:1484–1499. doi:10.1016/j.joca.2012.08.027.
  • Scanzello CR, Goldring SR. The role of synovitis in osteoarthritis pathogenesis. Bone. 2012;51:249–257. doi:10.1016/j.bone.2012.02.012.
  • Brandt KD, Radin EL, Dieppe PA, et al. Yet more evidence that osteoarthritis is not a cartilage disease. Ann Rheum Dis. 2006;65:1261–1264. doi:10.1136/ard.2006.058347.
  • Hunziker EB, Lippuner K, Keel MJ, et al. An educational review of cartilage repair: precepts & practice–myths & misconceptions–progress & prospects. Osteoarthr Cartil. 2015;23:334–350. doi:10.1016/j.joca.2014.12.011.
  • Pridie K, Gordon G. A method of resurfacing osteoarthritic knee joints. J Bone Joint Surgery British Vol. 1959;41:618–619.
  • Radin EL, Rose RM Role of subchondral bone in the initiation and progression of cartilage damage. Clin Orthop Relat Res. 1986;213:34–40.
  • Lajeunesse D, Reboul P. Subchondral bone in osteoarthritis: a biologic link with articular cartilage leading to abnormal remodeling. Curr Opin Rheumatol. 2003;15:628–633.
  • Bellido M, Lugo L, Roman-Blas JA, et al. Improving subchondral bone integrity reduces progression of cartilage damage in experimental osteoarthritis preceded by osteoporosis. Osteoarthr Cartil. 2011;19:1228–1236. doi:10.1016/j.joca.2011.07.003.
  • Lajeunesse D. Subchondral bone involvement in the pathophysiology of osteoarthritis. In: Understanding Osteoarthritis from bench to bedside. Kerala: Research Signpost. 2011. p. 69–83.
  • Pan J, Wang B, Li W, et al. Elevated cross-talk between subchondral bone and cartilage in osteoarthritic joints. Bone. 2012;51:212–217. doi:10.1016/j.bone.2011.11.030.
  • Suri S, Walsh DA. Osteochondral alterations in osteoarthritis. Bone. 2012;51:204–211. doi:10.1016/j.bone.2011.10.010.
  • Martel-Pelletier J, Wildi LM, Pelletier J-P. Future therapeutics for osteoarthritis. Bone. 2012;51:297–311. doi:10.1016/j.bone.2011.10.008.
  • Sanchez M, Fiz N, Azofra J, et al.. A randomized clinical trial evaluating plasma rich in growth factors (PRGF-Endoret) versus hyaluronic acid in the short-term treatment of symptomatic knee osteoarthritis. Arthroscopy. 2012;28:1070–1078. doi:10.1016/j.arthro.2012.05.011.
  • Filardo G, Kon E, Pereira Ruiz MT, et al. Platelet-rich plasma intra-articular injections for cartilage degeneration and osteoarthritis: single- versus double-spinning approach. Knee Surg Sports Traumatol Arthrosc. 2012;20:2082–2091. doi:10.1007/s00167-011-1837-x.
  • Vaquerizo V, Plasencia MA, Arribas I, et al. Comparison of intra-articular injections of plasma rich in growth factors (PRGF-Endoret) versus Durolane hyaluronic acid in the treatment of patients with symptomatic osteoarthritis: a randomized controlled trial. Arthroscopy. 2013;29:1635–1643. doi:10.1016/j.arthro.2013.07.264.
  • Bendinelli P, Matteucci E, Dogliotti G, et al.. Molecular basis of anti-inflammatory action of platelet-rich plasma on human chondrocytes: mechanisms of NF-kappaB inhibition via HGF. J Cell Physiol. 2010;225:757–766. doi:10.1002/jcp.22274.
  • Van Buul GM, Koevoet WL, Kops N, et al. Platelet-rich plasma releasate inhibits inflammatory processes in osteoarthritic chondrocytes. Am J Sports Med. 2011;39:2362–2370. doi:10.1177/0363546511419278.
  • Montaseri A, Busch F, Mobasheri A, et al. IGF-1 and PDGF-bb suppress IL-1beta-induced cartilage degradation through down-regulation of NF-kappaB signaling: involvement of Src/PI-3K/AKT pathway. PLoS One. 2011;6:e28663. doi:10.1371/journal.pone.0028663.
  • Coudriet GM, He J, Trucco M, et al. Hepatocyte growth factor modulates interleukin-6 production in bone marrow derived macrophages: implications for inflammatory mediated diseases. PLoS One. 2010;5:e15384. doi:10.1371/journal.pone.0015384.
  • Sundman EA, Cole BJ, Karas V, et al. The anti-inflammatory and matrix restorative mechanisms of platelet-rich plasma in osteoarthritis. Am J Sports Med. 2014;42:35–41. doi:10.1177/0363546513507766.
  • Tohidnezhad M, Wruck CJ, Slowik A, et al. Role of platelet-released growth factors in detoxification of reactive oxygen species in osteoblasts. Bone. 2014;65:9–17. doi:10.1016/j.bone.2014.04.029.
  • Liu HY, Wu AT, Tsai CY, et al. The balance between adipogenesis and osteogenesis in bone regeneration by platelet-rich plasma for age-related osteoporosis. Biomaterials. 2011;32:6773–6780. doi:10.1016/j.biomaterials.2011.05.080.
  • Liu HY, Huang CF, Lin TC, et al. Delayed animal aging through the recovery of stem cell senescence by platelet rich plasma. Biomaterials. 2014;35:9767–9776. doi:10.1016/j.biomaterials.2014.08.034.
  • Descalzi F, Ulivi V, Cancedda R, et al. Platelet-rich plasma exerts antinociceptive activity by a peripheral endocannabinoid-related mechanism. Tissue Eng Part A. 2013;19:2120–2129. doi:10.1089/ten.TEA.2012.0557.
  • Wu CC, Chen WH, Zao B, et al. Regenerative potentials of platelet-rich plasma enhanced by collagen in retrieving pro-inflammatory cytokine-inhibited chondrogenesis. Biomaterials. 2011;32:5847–5854. doi:10.1016/j.biomaterials.2011.05.002.
  • Spreafico A, Chellini F, Frediani B, et al. Biochemical investigation of the effects of human platelet releasates on human articular chondrocytes. J Cell Biochem. 2009;108:1153–1165. doi:10.1002/jcb.22344.
  • Anitua E, Sanchez M, Nurden AT, et al. Platelet-released growth factors enhance the secretion of hyaluronic acid and induce hepatocyte growth factor production by synovial fibroblasts from arthritic patients. Rheumatology (Oxford). 2007;46:1769–1772. doi:10.1093/rheumatology/kem234.
  • Sakata R, McNary SM, Miyatake K, et al. Stimulation of the superficial zone protein and lubrication in the articular cartilage by human platelet-rich plasma. Am J Sports Med. 2015;43:1467–1473. doi:10.1177/0363546515575023.
  • Buchman TG. The community of the self. Nature. 2002;420:246–251. doi:10.1038/nature01260.
  • Yokota H, Leong DJ, Sun HB. Mechanical loading: bone remodeling and cartilage maintenance. Curr Osteoporos Rep. 2011;9:237–242. doi:10.1007/s11914-011-0067-y.
  • Nam J, Aguda BD, Rath B, et al. Biomechanical thresholds regulate inflammation through the NF-kappaB pathway: experiments and modeling. PLoS One. 2009;4:e5262. doi:10.1371/journal.pone.0005262.
  • Karsdal MA, Bay-Jensen AC, Lories RJ, et al.. The coupling of bone and cartilage turnover in osteoarthritis: opportunities for bone antiresorptives and anabolics as potential treatments?. Ann Rheum Dis. 2014;73:336–348. doi:10.1136/annrheumdis-2013-204111.
  • Sanchez C, Pesesse L, Gabay O, et al. Regulation of subchondral bone osteoblast metabolism by cyclic compression. Arthritis Rheum. 2012;64:1193–1203. doi:10.1002/art.33445.
  • Liu-Bryan R, Terkeltaub R. Emerging regulators of the inflammatory process in osteoarthritis. Nat Rev Rheumatol. 2015;11:35–44. doi:10.1038/nrrheum.2014.162.
  • Berenbaum F. Osteoarthritis as an inflammatory disease (osteoarthritis is not osteoarthrosis!). Osteoarthr Cartil. 2013;21:16–21. doi:10.1016/j.joca.2012.11.012.
  • Scanzello CR, Plaas A, Crow MK. Innate immune system activation in osteoarthritis: is osteoarthritis a chronic wound?. Curr Opin Rheumatol. 2008;20:565–572. doi:10.1097/BOR.0b013e32830aba34.
  • Stolz M, Gottardi R, Raiteri R, et al. Early detection of aging cartilage and osteoarthritis in mice and patient samples using atomic force microscopy. Nat Nanotechnol. 2009;4:186–192. doi:10.1038/nnano.2008.410.
  • Goldring MB, Otero M, Plumb DA, et al. Roles of inflammatory and anabolic cytokines in cartilage metabolism: signals and multiple effectors converge upon MMP-13 regulation in osteoarthritis. Eur Cell Mater. 2011;21:202–220.
  • Nathan C. Neutrophils and immunity: challenges and opportunities. Nat Rev Immunol. 2006;6:173–182. doi:10.1038/nri1785.
  • Kapoor M, Martel-Pelletier J, Lajeunesse D, et al. Role of proinflammatory cytokines in the pathophysiology of osteoarthritis. Nat Rev Rheumatol. 2011;7:33–42. doi:10.1038/nrrheum.2010.196.
  • Sellam J, Berenbaum F. The role of synovitis in pathophysiology and clinical symptoms of osteoarthritis. Nat Rev Rheumatol. 2010;6:625–635. doi:10.1038/nrrheum.2010.159.
  • Henrotin Y, Pesesse L, Sanchez C. Subchondral bone and osteoarthritis: biological and cellular aspects. Osteoporos Int. 2012;23(Suppl 8):S847–51. doi:10.1007/s00198-012-2162-z.
  • Sanchez C, Deberg MA, Bellahcene A, et al. Phenotypic characterization of osteoblasts from the sclerotic zones of osteoarthritic subchondral bone. Arthritis Rheum. 2008;58:442–455. doi:10.1002/art.23159.
  • Burr DB. The importance of subchondral bone in the progression of osteoarthritis. J Rheumatol Suppl. 2004;70:77–80.
  • Malinin T, Ouellette EA. Articular cartilage nutrition is mediated by subchondral bone: a long-term autograft study in baboons. Osteoarthr Cartil. 2000;8:483–491. doi:10.1053/joca.1999.0324.
  • Imhof H, Sulzbacher I, Grampp S, et al.. Subchondral bone and cartilage disease: a rediscovered functional unit. Invest Radiol. 2000;35:581–588.
  • Radin EL, Burr DB, Caterson B, et al. Mechanical determinants of osteoarthrosis. Semin Arthritis Rheum. 1991;21:12–21.
  • Barr AJ, Campbell TM, Hopkinson D, et al. A systematic review of the relationship between subchondral bone features, pain and structural pathology in peripheral joint osteoarthritis. Arthritis Res Ther. 2015;17:228. doi:10.1186/s13075-015-0735-x.
  • Marcu KB, Otero M, Olivotto E, et al. NF-kappaB signaling: multiple angles to target OA. Curr Drug Targets. 2010;11:599–613.
  • Goldring MB, Marcu KB. Cartilage homeostasis in health and rheumatic diseases. Arthritis Res Ther. 2009;11:224. doi:10.1186/ar2684.
  • Wang Q, Rozelle AL, Lepus CM, et al. Identification of a central role for complement in osteoarthritis. Nat Med. 2011;17:1674–1679. doi:10.1038/nm.2543.
  • Malfait AM, Schnitzer TJ. Towards a mechanism-based approach to pain management in osteoarthritis. Nat Rev Rheumatol. 2013;9:654–664. doi:10.1038/nrrheum.2013.138.
  • Matsukura Y, Muneta T, Tsuji K, et al. Mouse synovial mesenchymal stem cells increase in yield with knee inflammation. J Orthop Res. 2015;33:246–253. doi:10.1002/jor.22753.
  • Sekiya I, Ojima M, Suzuki S, et al. Human mesenchymal stem cells in synovial fluid increase in the knee with degenerated cartilage and osteoarthritis. J Orthop Res. 2012;30:943–949. doi:10.1002/jor.22029.
  • Jones EA, Crawford A, English A, et al. Synovial fluid mesenchymal stem cells in health and early osteoarthritis: detection and functional evaluation at the single-cell level. Arthritis Rheum. 2008;58:1731–1740. doi:10.1002/art.23485.
  • Zhang J, Middleton KK, Fu FH, et al. HGF mediates the anti-inflammatory effects of PRP on injured tendons. PLoS One. 2013;8:e67303. doi:10.1371/journal.pone.0067303.
  • Koelling S, Kruegel J, Irmer M, et al. Migratory chondrogenic progenitor cells from repair tissue during the later stages of human osteoarthritis. Cell Stem Cell. 2009;4:324–335. doi:10.1016/j.stem.2009.01.015.
  • Seol D, McCabe DJ, Choe H, et al. Chondrogenic progenitor cells respond to cartilage injury. Arthritis Rheum. 2012;64:3626–3637. doi:10.1002/art.34613.
  • Barry F, Murphy M. Mesenchymal stem cells in joint disease and repair. Nat Rev Rheumatol. 2013;9:584–594. doi:10.1038/nrrheum.2013.109.
  • Lee DH, Sonn CH, Han SB, et al. Synovial fluid CD34(-) CD44(+) CD90(+) mesenchymal stem cell levels are associated with the severity of primary knee osteoarthritis. Osteoarthr Cartil. 2012;20:106–109. doi:10.1016/j.joca.2011.11.010.
  • Pretzel D, Linss S, Rochler S, et al. Relative percentage and zonal distribution of mesenchymal progenitor cells in human osteoarthritic and normal cartilage. Arthritis Res Ther. 2011;13:R64. doi:10.1186/ar3320.
  • Singer NG, Caplan AI. Mesenchymal stem cells: mechanisms of inflammation. Annu Rev Pathol. 2011;6:457–478. doi:10.1146/annurev-pathol-011110-130230.
  • Zhao W, Wang T, Luo Q, et al.. Cartilage degeneration and excessive subchondral bone formation in spontaneous osteoarthritis involves altered TGF‐β signaling. J Orthopaedic Res. 2015. doi:10.1002/jor.23079.
  • Radin EL, Paul IL, Rose RM. Role of mechanical factors in pathogenesis of primary osteoarthritis. Lancet. 1972;1:519–522.
  • Neuss S, Schneider RK, Tietze L, et al. Secretion of fibrinolytic enzymes facilitates human mesenchymal stem cell invasion into fibrin clots. Cells Tissues Organs. 2010;191:36–46. doi:10.1159/000215579.
  • Burr DB, Gallant MA. Bone remodelling in osteoarthritis. Nat Rev Rheumatol. 2012;8:665–673. doi:10.1038/nrrheum.2012.130.
  • Mapp PI, Walsh DA. Mechanisms and targets of angiogenesis and nerve growth in osteoarthritis. Nat Rev Rheumatol. 2012;8:390–398. doi:10.1038/nrrheum.2012.80.
  • Guevremont M, Martel-Pelletier J, Massicotte F, et al. Human adult chondrocytes express hepatocyte growth factor (HGF) isoforms but not HgF: potential implication of osteoblasts on the presence of HGF in cartilage. J Bone Miner Res. 2003;18:1073–1081. doi:10.1359/jbmr.2003.18.6.1073.
  • Lyons TJ, McClure SF, Stoddart RW, et al. The normal human chondro-osseous junctional region: evidence for contact of uncalcified cartilage with subchondral bone and marrow spaces. BMC Musculoskelet Disord. 2006;7:52. doi:10.1186/1471-2474-7-52.
  • Zhen G, Wen C, Jia X, et al.. Inhibition of TGF-beta signaling in mesenchymal stem cells of subchondral bone attenuates osteoarthritis. Nat Med. 2013;19:704–712. doi:10.1038/nm.3143.
  • Burr DB, Radin EL. Microfractures and microcracks in subchondral bone: are they relevant to osteoarthrosis?. Rheum Dis Clin North Am. 2003;29:675–685.
  • Felson DT, Chaisson CE, Hill CL, et al. The association of bone marrow lesions with pain in knee osteoarthritis. Ann Intern Med. 2001;134:541–549.
  • Taljanovic MS, Graham AR, Benjamin JB, et al. Bone marrow edema pattern in advanced hip osteoarthritis: quantitative assessment with magnetic resonance imaging and correlation with clinical examination, radiographic findings, and histopathology. Skeletal Radiol. 2008;37:423–431. doi:10.1007/s00256-008-0446-3.
  • Hunter DJ, Gerstenfeld L, Bishop G, et al. Bone marrow lesions from osteoarthritis knees are characterized by sclerotic bone that is less well mineralized. Arthritis Res Ther. 2009;11:R11. doi:10.1186/ar2684.
  • Mapp PI, Avery PS, McWilliams DF, et al. Angiogenesis in two animal models of osteoarthritis. Osteoarthr Cartil. 2008;16:61–69. doi:10.1016/j.joca.2007.05.017.
  • Pan J, Zhou X, Li W, et al.. In situ measurement of transport between subchondral bone and articular cartilage. J Orthop Res. 2009;27:1347–1352. doi:10.1002/jor.20883.
  • Tat SK, Lajeunesse D, Pelletier J-P, et al. Targeting subchondral bone for treating osteoarthritis: what is the evidence?. Best Pract Res Clin Rheumatol. 2010;24:51–70. doi:10.1016/j.berh.2009.08.004.
  • Westacott CI, Webb GR, Warnock MG, et al. Alteration of cartilage metabolism by cells from osteoarthritic bone. Arthritis Rheum. 1997;40:1282–1291. doi:10.1002/1529-0131(199707)40:7<1282::AID-ART13>3.0.CO;2-E.
  • Hilal G, Martel-Pelletier J, Pelletier JP, et al. Osteoblast-like cells from human subchondral osteoarthritic bone demonstrate an altered phenotype in vitro: possible role in subchondral bone sclerosis. Arthritis Rheum. 1998;41:891–899. doi:10.1002/1529-0131(199805)41:5<891::AID-ART17>3.0.CO;2-X.
  • Sanchez C, Deberg MA, Piccardi N, et al. Osteoblasts from the sclerotic subchondral bone downregulate aggrecan but upregulate metalloproteinases expression by chondrocytes. This effect is mimicked by interleukin-6, −1beta and oncostatin M pre-treated non-sclerotic osteoblasts. Osteoarthr Cartil. 2005;13:979–987. doi:10.1016/j.joca.2005.03.008.
  • Sanchez C, Deberg MA, Piccardi N, et al. Subchondral bone osteoblasts induce phenotypic changes in human osteoarthritic chondrocytes. Osteoarthr Cartil. 2005;13:988–997. doi:10.1016/j.joca.2005.07.012.
  • Grano M, Galimi F, Zambonin G, et al. Hepatocyte growth factor is a coupling factor for osteoclasts and osteoblasts in vitro. Proc Natl Acad Sci USA. 1996;93:7644–7648.
  • Stella MC, Comoglio PM. HGF: a multifunctional growth factor controlling cell scattering. Int J Biochem Cell Biol. 1999;31:1357–1362.
  • Davidson EB, Van Caam A, Vitters E, et al. TGF-β is a potent inducer of nerve growth factor in articular cartilage via the ALK5-Smad2/3 pathway. Potential Role in OA Related Pain? Osteoarthr Cartil. 2015;23:478–486. doi:10.1016/j.joca.2014.12.005.
  • Scharstuhl A, Schewe B, Benz K, et al. Chondrogenic potential of human adult mesenchymal stem cells is independent of age or osteoarthritis etiology. Stem Cells. 2007;25:3244–3251. doi:10.1634/stemcells.2007-0300.
  • Roubille C, Pelletier J-P, Martel-Pelletier J. New and emerging treatments for osteoarthritis management: will the dream come true with personalized medicine?. Expert Opin Pharmacother. 2013;14:2059–2077. doi:10.1517/14656566.2013.825606.
  • Nurden AT, Nurden P, Sanchez M, et al. Platelets and wound healing. Front Biosci. 2008;13:3532–3548.
  • DeLong JM, Russell RP, Mazzocca AD. Platelet-rich plasma: the PAW classification system. Arthroscopy. 2012;28:998–1009. doi:10.1016/j.arthro.2012.04.148.
  • Wasterlain AS, Braun HJ, Dragoo JL. Contents and formulations of platelet-rich plasma. Oper Tech Orthop. 2012;22:33–42. doi:10.1053/j.oto.2011.11.001.
  • Castillo TN, Pouliot MA, Kim HJ, et al. Comparison of growth factor and platelet concentration from commercial platelet-rich plasma separation systems. Am J Sports Med. 2011;39:266–271. doi:10.1177/0363546510387517.
  • Metcalf KB, Mandelbaum BR, McIlwraith CW. Application of platelet-rich plasma to disorders of the knee joint. Cartilage. 2013;4:295–312. doi:10.1177/1947603513487553.
  • Kreuz PC, Kruger JP, Metzlaff S, et al.. Platelet-rich plasma preparation types show impact on chondrogenic differentiation, migration, and proliferation of human subchondral mesenchymal progenitor cells. Arthroscopy. 2015;31:1951–1961. doi:10.1016/j.arthro.2015.03.033.
  • Anitua E, Prado R, Azkargorta M, et al. High-throughput proteomic characterization of plasma rich in growth factors (PRGF-Endoret)-derived fibrin clot interactome. J Tissue Eng Regen Med. 2015;9:E1–E12. doi:10.1002/term.1721.
  • Nurden AT. Platelets, inflammation and tissue regeneration. Thromb Haemost. 2011;105(Suppl 1):S13–33. doi:10.1160/THS10-11-0720.
  • Martino MM, Briquez PS, Guc E, et al. Growth factors engineered for super-affinity to the extracellular matrix enhance tissue healing. Science. 2014;343:885–888. doi:10.1126/science.1247663.
  • Shworak NW. Heparan Sulfate in Endothelial biomedicine; 947-59. WC Aird, Endothelial Medicine. Cambridge: Cambridge University Press; 2007.
  • Engler AJ, Sen S, Sweeney HL, et al. Matrix elasticity directs stem cell lineage specification. Cell. 2006;126:677–689. doi:10.1016/j.cell.2006.06.044.
  • Sánchez M, Fiz N, Guadilla J, et al.. Intraosseous infiltration of platelet-rich plasma for severe knee osteoarthritis. Arthrosc Tech. 2014. doi:10.1016/j.eats.2014.09.006.
  • Anitua E, Zalduendo MM, Prado R, et al. Morphogen and proinflammatory cytokine release kinetics from PRGF-Endoret fibrin scaffolds: evaluation of the effect of leukocyte inclusion. J Biomed Mater Res A. 2015;103:1011–1020. doi:10.1002/jbm.a.35244.
  • Anitua E, Sanchez M, Orive G, et al. A biological therapy to osteoarthritis treatment using platelet-rich plasma. Expert Opin Biol Ther. 2013;13:1161–1172. doi:10.1517/14712598.2013.801450.
  • Magalon J, Bausset O, Serratrice N, et al. Characterization and comparison of 5 platelet-rich plasma preparations in a single-donor model. Arthroscopy. 2014;30:629–638. doi:10.1016/j.arthro.2014.02.020.
  • Tidball JG. Inflammatory processes in muscle injury and repair. Am J Physiol Regul Integr Comp Physiol. 2005;288:R345–53. doi:10.1152/ajpregu.00454.2004.
  • Braun HJ, Kim HJ, Chu CR, et al. The effect of platelet-rich plasma formulations and blood products on human synoviocytes: implications for intra-articular injury and therapy. Am J Sports Med. 2014;42:1204–1210. doi:10.1177/0363546514525593.
  • Assirelli E, Filardo G, Mariani E, et al.. Effect of two different preparations of platelet-rich plasma on synoviocytes. Knee Surg Sports Traumatol Arthrosc. 2014.
  • Cavallo C, Filardo G, Mariani E, et al.. Comparison of platelet-rich plasma formulations for cartilage healing: an in vitro study. J Bone Joint Surg Am. 2014;96:423–429. doi:10.2106/JBJS.M.00726.
  • Anitua E, Prado R, Orive G. Closing regulatory gaps: new ground rules for platelet-rich plasma. Trends Biotechnol. 2015;33:492–495. doi:10.1016/j.tibtech.2015.07.002.
  • Renn TY, Kao YH, Wang CC, et al.. Anti-inflammatory effects of platelet biomaterials in a macrophage cellular model. Vox Sang. 2015. doi:10.1111/vox.12264.
  • Vasina EM, Cauwenberghs S, Feijge MA, et al. Microparticles from apoptotic platelets promote resident macrophage differentiation. Cell Death Dis. 2011;2:e211. doi:10.1038/cddis.2011.82.
  • Fahy N, De Vries-Van Melle ML, Lehmann J, et al. Human osteoarthritic synovium impacts chondrogenic differentiation of mesenchymal stem cells via macrophage polarisation state. Osteoarthr Cartil. 2014;22:1167–1175. doi:10.1016/j.joca.2014.05.021.
  • Fahy N, Farrell E, Ritter T, et al. Immune modulation to improve tissue engineering outcomes for cartilage repair in the osteoarthritic joint. Tissue Eng Part B Rev. 2015;21:55–66. doi:10.1089/ten.TEB.2014.0098.
  • Anitua E, Zalduendo M, Troya M, et al. Leukocyte inclusion within a platelet rich plasma-derived fibrin scaffold stimulates a more pro-inflammatory environment and alters fibrin properties. PLoS One. 2015;10:e0121713. doi:10.1371/journal.pone.0121713.
  • Xie X, Ulici V, Alexander PG, et al. Platelet-rich plasma inhibits mechanically induced injury in chondrocytes. Arthroscopy. 2015;31:1142–1150. doi:10.1016/j.arthro.2015.01.007.
  • Kubota S, Kawata K, Yanagita T, et al. Abundant retention and release of connective tissue growth factor (CTGF/CCN2) by platelets. J Biochem. 2004;136:279–282. doi:10.1093/jb/mvh126.
  • Itoh S, Hattori T, Tomita N, et al. CCN family member 2/connective tissue growth factor (CCN2/CTGF) has anti-aging effects that protect articular cartilage from age-related degenerative changes. PLoS One. 2013;8:e71156. doi:10.1371/journal.pone.0071156.
  • Goldring MB, Berenbaum F. Emerging targets in osteoarthritis therapy. Curr Opin Pharmacol. 2015;22:51–63. doi:10.1016/j.coph.2015.03.004.
  • Lotz M, Loeser RF. Effects of aging on articular cartilage homeostasis. Bone. 2012;51:241–248. doi:10.1016/j.bone.2012.03.023.
  • Dragoo JL, Korotkova T, Wasterlain AS, et al. Age-related changes of chondrogenic growth factors in platelet-rich plasma. Oper Tech Orthop. 2012;22:49–55. doi:10.1053/j.oto.2011.11.004.
  • Do Amaral RJ, Matsiko A, Tomazette MR, et al, Platelet-rich plasma releasate differently stimulates cellular commitment toward the chondrogenic lineage according to concentration. J Tissue Eng. 2015;6:2041731415594127. doi:10.1177/2041731415594127.
  • Lee HR, Park KM, Joung YK, et al. Platelet-rich plasma loaded hydrogel scaffold enhances chondrogenic differentiation and maturation with up-regulation of CB1 and CB2. J Control Release. 2012;159:332–337. doi:10.1016/j.jconrel.2012.02.008.
  • Kruger JP, Hondke S, Endres M, et al. Human platelet-rich plasma stimulates migration and chondrogenic differentiation of human subchondral progenitor cells. J Orthop Res. 2012;30:845–852. doi:10.1002/jor.22005.
  • Kruger JP, Ketzmar AK, Endres M, et al. Human platelet-rich plasma induces chondrogenic differentiation of subchondral progenitor cells in polyglycolic acid-hyaluronan scaffolds. J Biomed Mater Res B Appl Biomater. 2014;102:681–692. doi:10.1002/jbm.b.33047.
  • Anitua E, Sanchez M, Nurden AT, et al. Reciprocal actions of platelet-secreted TGF-beta1 on the production of VEGF and HGF by human tendon cells. Plast Reconstr Surg. 2007;119:950–959. doi:10.1097/01.prs.0000255543.43695.1d.
  • Anitua E, Sanchez M, Merayo-Lloves J, et al. Plasma rich in growth factors (PRGF-Endoret) stimulates proliferation and migration of primary keratocytes and conjunctival fibroblasts and inhibits and reverts TGF-beta1-Induced myodifferentiation. Invest Ophthalmol Vis Sci. 2011;52:6066–6073. doi:10.1167/iovs.11-7302.
  • Anitua E, Andia I, Sanchez M, et al. Autologous preparations rich in growth factors promote proliferation and induce VEGF and HGF production by human tendon cells in culture. J Orthop Res. 2005;23:281–286. doi:10.1016/j.orthres.2004.08.015.
  • Anitua E, Sanchez M, De La Fuente M, et al. Plasma rich in growth factors (PRGF-Endoret) stimulates tendon and synovial fibroblasts migration and improves the biological properties of hyaluronic acid. Knee Surg Sports Traumatol Arthrosc. 2012;20:1657–1665. doi:10.1007/s00167-011-1697-4.
  • Sanchez M, Guadilla J, Fiz N, et al. Ultrasound-guided platelet-rich plasma injections for the treatment of osteoarthritis of the hip. Rheumatology (Oxford). 2012;51:144–150. doi:10.1093/rheumatology/ker303.
  • Richardson D, Pearson RG, Kurian N, et al. Characterisation of the cannabinoid receptor system in synovial tissue and fluid in patients with osteoarthritis and rheumatoid arthritis. Arthritis Res Ther. 2008;10:R43. doi:10.1186/ar2401.
  • Kulawig R, Kruger JP, Klein O, et al. Identification of fibronectin as a major factor in human serum to recruit subchondral mesenchymal progenitor cells. Int J Biochem Cell Biol. 2013;45:1410–1418. doi:10.1016/j.biocel.2013.04.016.
  • Anitua E, Sanchez M, Nurden AT, et al. Autologous fibrin matrices: a potential source of biological mediators that modulate tendon cell activities. J Biomed Mater Res A. 2006;77:285–293. doi:10.1002/jbm.a.30585.
  • Sanchez M, Anitua E, Azofra J, et al. Ligamentization of tendon grafts treated with an endogenous preparation rich in growth factors: gross morphology and histology. Arthroscopy. 2010;26:470–480. doi:10.1016/j.arthro.2009.08.019.
  • Hayami T, Pickarski M, Wesolowski GA, et al. The role of subchondral bone remodeling in osteoarthritis: reduction of cartilage degeneration and prevention of osteophyte formation by alendronate in the rat anterior cruciate ligament transection model. Arthritis Rheum. 2004;50:1193–1206. doi:10.1002/art.20124.
  • Lampropoulou-Adamidou K, Dontas I, Stathopoulos IP, et al. Chondroprotective effect of high-dose zoledronic acid: an experimental study in a rabbit model of osteoarthritis. J Orthop Res. 2014;32:1646–1651. doi:10.1002/jor.22712.
  • Sagar DR, Ashraf S, Xu L, et al. Osteoprotegerin reduces the development of pain behaviour and joint pathology in a model of osteoarthritis. Ann Rheum Dis. 2014;73:1558–1565. doi:10.1136/annrheumdis-2013-203260.
  • Pelletier JP, Kapoor M, Fahmi H, et al. Strontium ranelate reduces the progression of experimental dog osteoarthritis by inhibiting the expression of key proteases in cartilage and of IL-1beta in the synovium. Ann Rheum Dis. 2013;72:250–257. doi:10.1136/annrheumdis-2012-201710.
  • Davis AJ, Smith TO, Hing CB, et al. Are bisphosphonates effective in the treatment of osteoarthritis pain? A meta-analysis and systematic review. PLoS One. 2013;8:e72714. doi:10.1371/journal.pone.0072714.
  • Laslett LL, Dore DA, Quinn SJ, et al. Zoledronic acid reduces knee pain and bone marrow lesions over 1 year: a randomised controlled trial. Ann Rheum Dis. 2012;71:1322–1328. doi:10.1136/annrheumdis-2011-200970.
  • Laslett LL, Kingsbury SR, Hensor EM, et al. Effect of bisphosphonate use in patients with symptomatic and radiographic knee osteoarthritis: data from the osteoarthritis initiative. Ann Rheum Dis. 2014;73:824–830. doi:10.1136/annrheumdis-2012-202989.
  • Reginster JY, Badurski J, Bellamy N, et al. Efficacy and safety of strontium ranelate in the treatment of knee osteoarthritis: results of a double-blind, randomised placebo-controlled trial. Ann Rheum Dis. 2013;72:179–186. doi:10.1136/annrheumdis-2012-202231.
  • Pelletier JP, Roubille C, Raynauld JP, et al. Disease-modifying effect of strontium ranelate in a subset of patients from the Phase III knee osteoarthritis study SEKOIA using quantitative MRI: reduction in bone marrow lesions protects against cartilage loss. Ann Rheum Dis. 2015;74:422–429. doi:10.1136/annrheumdis-2013-203989.
  • Philippart P, Meuleman N, Stamatopoulos B, et al. In vivo production of mesenchymal stromal cells after injection of autologous platelet-rich plasma activated by recombinant human soluble tissue factor in the bone marrow of healthy volunteers. Tissue Eng Part A. 2014;20:160–170. doi:10.1089/ten.TEA.2013.0244.
  • Wang-Saegusa A, Cugat R, Ares O, et al. Infiltration of plasma rich in growth factors for osteoarthritis of the knee short-term effects on function and quality of life. Arch Orthop Trauma Surg. 2011;131:311–317. doi:10.1007/s00402-010-1167-3.
  • Diego Delgado PS, Muiños E, Paiva B, et al. Phase II Clinical trial of intraosseous platelet rich plasma infiltration for severe knee osteoarthritis: preliminary results at 2 months. 2015. ICRS 2015 Chicago
  • Sánchez M, Delgado D, Sánchez P, et al.. Platelet rich plasma and knee surgery. Biomed Res Int. 2014;2014. doi:10.1155/2014/890630.
  • Evans CH, Kraus VB, Setton LA. Progress in intra-articular therapy. Nat Rev Rheumatol. 2014;10:11–22. doi:10.1038/nrrheum.2013.159.
  • Kang ML, Im G-I. Drug delivery systems for intra-articular treatment of osteoarthritis. Expert Opin Drug Deliv. 2014;11:269–282. doi:10.1517/17425247.2014.867325.
  • Sanchez M, Anitua E, Cugat R, et al. Nonunions treated with autologous preparation rich in growth factors. J Orthop Trauma. 2009;23:52–59. doi:10.1097/BOT.0b013e31818faded.
  • Kyllonen L, D’Este M, Alini M, et al. Local drug delivery for enhancing fracture healing in osteoporotic bone. Acta Biomater. 2015;11:412–434. doi:10.1016/j.actbio.2014.09.006.
  • Conboy I, Freimer J, Weisenstein L. 5.526 - Tissue engineering of muscle tissue. In: Ducheyne P, editor. Comprehensive biomaterials. Oxford: Elsevier; 2011. p. 345–359.
  • Seidel MF, Herguijuela M, Forkert R, et al. Nerve growth factor in rheumatic diseases. Semin Arthritis Rheum. 2010;40:109–126. doi:10.1016/j.semarthrit.2009.03.002.
  • Schippinger G, Fankhauser F, Oettl K, et al. Does single intramuscular application of autologous conditioned plasma influence systemic circulating growth factors?. J Sports Sci Med. 2012;11:551–556.
  • Wasterlain AS, Braun HJ, Harris AH, et al. The systemic effects of platelet-rich plasma injection. Am J Sports Med. 2013;41:186–193. doi:10.1177/0363546512466383.

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.