Platelet Rich Plasma for the management of knee osteoarthritis: a review of biological role and potential mechanism of action
Keywords:
platelet-rich plasma, osteoarthritis, knee, PRPAbstract
Knee osteoarthritis (KOA) is a progressive degenerative disease characterised by joint cartilage damage, interindividual variation in clinical manifestations and severe end-stage clinical symptoms. It is one of the most common arthritis types, with increasing prevalence as life expectancy and obesity rise. It is quite a significant public health issue as it reduces physical function, causes chronic pain, and severely impacts the quality of life. The early and middle KOA stages are usually managed conservatively, and the end-stage KOA with knee arthroplasty. Emerging evidence suggests that platelet-rich plasma (PRP) has a potentially regenerative effect on various tissues. Intraarticular PRP has been shown to provide symptomatic relief in early KOA, at least as effective as hyaluronic acid and steroid injections. The combined effects of PRP positively impact inflammation, angiogenesis, cell migration and metabolism of many degenerative joints. However, the PRP’s biological activity and mechanism of action are not yet fully understood. This article aims to resume the critical evidence highlighting all reported biological, biochemical and cellular PRP actions in KOA to help physicians better understand this molecular treatment type.
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References
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36. Ren H, Zhang S, Wang X, Li Z, Guo W. Role of platelet-rich plasma in the treatment of osteoarthritis: a meta-analysis. J Int Med Res. 2020; 48: 300060520964661.
37. Parrish WR, Roides B. Physiology of Blood Components in Wound Healing: an Appreciation of Cellular Co-Operativity in Platelet Rich Plasma Action. J Exerc Sports Orthop. 2017; 4: 1-14.
38. Vasina EM, Cauwenberghs S, Feijge MA, Heemskerk JW, Weber C, Koenen RR. Microparticles from apoptotic platelets promote resident macrophage differentiation. Cell Death Dis. 2011; 2: e211.
39. Lepetsos P, Papavassiliou AG. ROS/oxidative stress signaling in osteoarthritis. Biochim Biophys Acta. 2016; 1862: 576-591.
40. Khatab S, van Buul GM, Kops N, Bastiaansen-Jenniskens YM, Bos PK, Verhaar JA, et al. Intra-articular Injections of Platelet-Rich Plasma Releasate Reduce Pain and Synovial Inflammation in a Mouse Model of Osteoarthritis. Am J Sports Med. 2018; 46: 977-986.
41. Sundman EA, Cole BJ, Karas V, Della Valle C, Tetreault MW, Mohammed HO, et al. The anti-inflam
2. Allen KD, Thoma LM, Golightly YM. Epidemiology of osteoarthritis. Osteoarthritis Cartilage 2022; 30: 184–195.
3. Southworth TM, Naveen NB, Tauro TM, Leong NL, Cole BJ. The Use of Platelet-Rich Plasma in Symptomatic Knee Osteoarthritis. J Knee Surg. 2019; 32: 37–45.
4. Mansfield JC, Mandalia V, Toms A, Winlove PC, Brasselet S. Collagen reorganization in cartilage under strain probed by polarization sensitive second harmonic generation microscopy. J R Soc Interface. 2019; 16: 20180611.
5. Goldring SR, Goldring MB. Changes in the osteochondral unit during osteoarthritis: Structure, function and cartilage bone crosstalk. Nat Rev Rheumatol. 2016; 12: 632–644.
6. Ruhlen R, Marberry K. The chondrocyte primary cilium. Osteoarthritis Cartilage 2014; 22: 1071–1076.
7. Wang X, Khalil RA. Matrix Metalloproteinases, Vascular Remodeling, and Vascular Disease. Adv Pharmacol. 2018; 81: 241-330.
8. Funck-Brentano T, Cohen-Solal M. Subchondral bone and osteoarthritis. Curr Opin Rheumatol. 2015; 27: 420–426.
9. Griffin TM, Scanzello CR. Innate Inflammation and Synovial Macrophages in Osteoarthritis Pathophysiology. Clin Exp Rheumatol. 2019; Suppl 120: 57-63.
10. Yang F, Zhou S, Wang C, Huang Y, Li H, Wang Y, et al. Epigenetic modifications of interleukin-6 in synovial fibroblasts from osteoarthritis patients. Sci Rep. 2017; 7: 43592.
11. Zhu Z, Otahal P, Wang B, Jin X, Laslett LL, Wluka AE, et al. Cross-sectional and longitudinal associations between serum inflammatory cytokines and knee bone marrow lesions in patients with knee osteoarthritis. Osteoarthritis Cartilage. 2017; 25: 499–505.
12. Boehme KA, Rolauffs B. Onset and progression of human osteoarthritis—Can growth factors, inflammatory cytokines, or differential miRNA expression concomitantly induce proliferation, ECM degradation, and inflammation in articular cartilage? Int J Mol Sci. 2018; 19: 2282.
13. Yang Q, Zhou Y, Cai P, Fu W, Wang J, Wei Q, et al. Up-regulated HIF-2α contributes to the Osteoarthritis development through mediating the primary cilia loss. Int Immunopharmacol. 2019; 75: 105762.
14. Nguyen LT, Sharma AR, Chakraborty C, Saibaba B, Ahn ME, Lee SS. Review of prospects of biological fluid biomarkers in osteoarthritis. Int J Mol Sci. 2017; 18: 601.
15. Heinegård D, Saxne T. The role of the cartilage matrix in osteoarthritis. Nat Rev Rheumatol. 2011; 7: 50–56.
16. Venkatesan JK, Rey-Rico A, Schmitt G, Wezel A, Madry H, Cucchiarini M. rAAV-mediated overexpression of TGF-β stably restructures human osteoarthritic articular cartilage in situ. J Transl Med. 2013; 11: 211.
17. Taniguchi Y, Yoshioka T, Kanamori A, Aoto K, Sugaya H, Yamazaki M. Intra-articular platelet-rich plasma (PRP) injections for treating knee pain associated with osteoarthritis of the knee in the Japanese population: A phase I and IIa clinical trial. Nagoya J Med Sci. 2018; 80: 39–51.
18. Boswell SG, Cole BJ, Sundman EA, Karas V, Fortier LA. Platelet-rich plasma: A milieu of bioactive factors. Arthroscopy. 2012; 28: 429-39.
19. Everts P, Onishi K, Jayaram P, Lana JF, Mautner K. Platelet-rich plasma: New performance understandings and therapeutic considerations in 2020. Int J Mol Sci. 2020; 21: 7794.
20. Asjid R, Faisal T, Qamar K, Khan SA, Khalil A, Zia MS. Platelet-rich Plasma-induced Inhibition of Chondrocyte Apoptosis Directly Affects Cartilage Thickness in Osteoarthritis. Cureus. 2019; 11: e6050.
21. Brandl A, Angele P, Roll C, Prantl L, Kujat R, Kinner B. Influence of the growth factors PDGF-BB, TGF-β1 and bFGF on the replicative aging of human articular chondrocytes during in vitro expansion. J Orthop Res. 2010; 28: 354–360.
22. Kapoor M, Martel-Pelletier J, Lajeunesse D, Pelletier JP, Fahmi H. Role of proinflammatory cytokines in the pathophysiology of osteoarthritis. Nat Rev Rheumatol. 2011; 7: 33–42.
23. Jedlitschky G, Tirschmann K, Lubenow LE, Nieuwenhuis HK, Akkerman JW, Greinacher A, et al. The nucleotide transporter MRP4 (ABCC4) is highly expressed in human platelets and present in dense granules, indicating a role in mediator storage. Blood. 2004; 104: 3603–3610.
24. Copie-Bergman C, Cuillière-Dartigues P, Baia M, Briere J, Delarue R, Canioni D, et al. MYC-IG rearrangements are negative predictors of survival in DLBCL patients treated with immunochemotherapy: A GELA/LYSA study. Blood. 2015; 126: 2466–2474.
25. Giusti I, D’Ascenzo S, Mancò A, Di Stefano G, Di Francesco M, Rughetti A, et al. Platelet Concentration in Platelet-Rich Plasma Affects Tenocyte Behavior in Vitro. Biomed Res Int. 2014; 2014: 630870.
26. Civinini R, Nistri L, Martini C, Redl B, Ristori G, Innocenti M. Growth factors in the treatment of early osteoarthritis. Clin Cases Miner Bone Metab. 2013; 10: 26-9.
27. Knezevic NN, Candido KD, Desai R, Kaye AD. Is Platelet-Rich Plasma a Future Therapy in Pain Management? Med Clin North Am. 2016; 100: 199-217.
28. Barrientos S, Stojadinovic O, Golinko MS, Brem H, Tomic-Canic M. Growth factors and cytokines in wound healing. Wound Repair Regen. 2008; 16: 585–601.
29. Drengk A, Zapf A, Stürmer EK, Stürmer KM, Frosch KH. Influence of platelet-rich plasma on chondrogenic differentiation and proliferation of chondrocytes and mesenchymal stem cells. Cells Tissues Organs. 2009; 189: 317–326.
30. Marques LF, Stessuk T, Camargo IC, Sabeh Junior N, dos Santos L, Ribeiro-Paes JT. Platelet-rich plasma (PRP): Methodological aspects and clinical applications. Platelets. 2015; 26: 101-13.
31. Van Pham P, Hong-Thien Bui K, Quoc Ngo D, Tan Khuat L, Kim Phan N. Transplantation of Nonexpanded Adipose Stromal Vascular Fraction and Platelet-Rich Plasma for Articular Cartilage Injury Treatment in Mice Model. J Med Eng. 2013; 2013: 832396.
32. Nikolidakis D, Jansen JA. The biology of platelet-rich plasma and its application in oral surgery: Literature review. Tissue Eng Part B Rev. 2008; 14: 249-58.
33. Andia I, Maffulli NA. contemporary view of platelet-rich plasma therapies: Moving toward refined clinical protocols and precise indications. Regen Med. 2018; 13: 717-728.
34. Spaková T, Rosocha J, Lacko M, Harvanová D, Gharaibeh A. Treatment of knee joint osteoarthritis with autologous platelet-rich plasma in comparison with hyaluronic acid. Am J Phys Med Rehabil. 2012; 91: 411-7.
35. Gosens T, Peerbooms JC, Van Laar W, Den Oudsten BL. Ongoing positive effect of platelet-rich plasma versus corticosteroid injection in lateral epicondylitis: A double-blind randomized controlled trial with 2-year follow-up. Am J Sports Med. 2011; 39: 1200-8.
36. Ren H, Zhang S, Wang X, Li Z, Guo W. Role of platelet-rich plasma in the treatment of osteoarthritis: a meta-analysis. J Int Med Res. 2020; 48: 300060520964661.
37. Parrish WR, Roides B. Physiology of Blood Components in Wound Healing: an Appreciation of Cellular Co-Operativity in Platelet Rich Plasma Action. J Exerc Sports Orthop. 2017; 4: 1-14.
38. Vasina EM, Cauwenberghs S, Feijge MA, Heemskerk JW, Weber C, Koenen RR. Microparticles from apoptotic platelets promote resident macrophage differentiation. Cell Death Dis. 2011; 2: e211.
39. Lepetsos P, Papavassiliou AG. ROS/oxidative stress signaling in osteoarthritis. Biochim Biophys Acta. 2016; 1862: 576-591.
40. Khatab S, van Buul GM, Kops N, Bastiaansen-Jenniskens YM, Bos PK, Verhaar JA, et al. Intra-articular Injections of Platelet-Rich Plasma Releasate Reduce Pain and Synovial Inflammation in a Mouse Model of Osteoarthritis. Am J Sports Med. 2018; 46: 977-986.
41. Sundman EA, Cole BJ, Karas V, Della Valle C, Tetreault MW, Mohammed HO, et al. The anti-inflam
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