Effect of Intra-Articular Injection of Platelet-Rich Plasma on the Serum Levels of Osteoarthritic Biomarkers in Patients with Unilateral Knee Osteoarthritis

Marek Lacko, Denisa Harvanová, Lucia Slovinská, Martin Matuška, Marek Balog, Antónia Lacková, Timea Špaková, Ján Rosocha, Marek Lacko, Denisa Harvanová, Lucia Slovinská, Martin Matuška, Marek Balog, Antónia Lacková, Timea Špaková, Ján Rosocha

Abstract

Background: The aim of this study is to determine the effect of three doses of intra-articular injection of platelet-rich plasma (PRP) into the osteoarthritic (OA) knee joint on the functional status and on the changes in the levels of specific OA biomarkers in blood serum.

Methods: Forty patients with unilateral primary knee osteoarthritis were enrolled in this single center, prospective clinical trial. For each patient, three intra-articular PRP injections were administered one week apart. Clinical and laboratory assessment was performed before the first PRP injection (baseline), and 3 months after the third PRP application (3-month follow up). Pain in the affected knee joint was assessed with the Visual Analog Scale for Pain (VAS). Change in clinical status was evaluated with the Western Ontario and McMaster Universities Arthritis Index Questionnaire (WOMAC). Concentrations of 19 biomarkers (EGF, Eotaxin, FGF-2, GRO, IL-10, IL-1RA, IL-8, IP-10, MCP-1, PDGF-AB/BB, RANTES, MMP-3, MMP-13, Collagen type 2, BMP-2, TIMP-1, TIMP-2, TGF beta 1, and COMP) in the serum of studied patients were quantified.

Results: At 3-month follow up, there was a significant decrease in the VAS score and significant improvement in the WOMAC score. There was a significant decrease in the levels of Eotaxin, MCP-1, MMP-1, IL-10, EGF, PDGF-AB/BB, TGF- β1 compared to baseline levels. A significant increase in markers BMP-2, COMP, Collagen type 2 and GRO was found at the same time point. There was no significant change in the concentrations of other biomarkers (FGF-2, IL-1RA, IL-8, IL-10, MMP-3, RANTES, TIMP-1, TIMP-3).

Conclusions: We found an increase in specific pro-anabolic and anti-inflammatory biomarkers with a concomitant decrease in pro-inflammatory biomarkers at 3 months after three intra-articular applications of PRP. Significant improvement in VAS and WOMAC scores was observed. Treatment with PRP may be an effective therapeutic option with anti-inflammatory and regenerative potential in patients with primary knee OA.

Keywords: biomarker; knee; osteoarthritis; platelet-rich plasma.

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Mean concentration of biomarkers before and 3 months after the treatment with PRP. Error bars indicate standard deviation; differences were analyzed using Student’s t-test; * p < 0.05.

References

    1. Aletaha D., Neogi T., Silman A.J., Funovits J., Felson D.T., Bingham C.O., 3rd, Birnbaum N.S., Burmester G.R., Bykerk V.P., Cohen M.D., et al. 2010 Rheumatoid arthritis classification criteria: An American College of Rheumatology/European League Against Rheumatism collaborative initiative. Ann. Rheum. Dis. 2010;69:1580–1588. doi: 10.1136/ard.2010.138461.
    1. Abramson S.B., Attur M. Developments in the scientific understanding of osteoarthritis. Arthritis Res. Ther. 2009;11:227. doi: 10.1186/ar2655.
    1. Tchetina E.V. Developmental Mechanisms in Articular Cartilage Degradation in Osteoarthritis. Arthritis. 2010;2011:683970. doi: 10.1155/2011/683970.
    1. dos Santos R.G., Santos G.S., Alkass N., Chiesa T.L., Azzini G.O., da Fonseca L.F., dos Santos A.F., Rodrigues B.L., Mosaner T., Lana J.F. The regenerative mechanisms of platelet-rich plasma: A review. Cytokine. 2021;144:155560. doi: 10.1016/j.cyto.2021.155560.
    1. Collins T., Alexander D., Barkatali B. Platelet-rich plasma: A narrative review. EFORT Open Rev. 2021;6:225–235. doi: 10.1302/2058-5241.6.200017.
    1. Gato-Calvo L., Magalhães J., Ruiz-Romero C., Blanco F.J., Burguera E.F. Platelet-rich plasma in osteoarthritis treatment: Review of current evidence. Ther. Adv. Chronic Dis. 2019;10:2040622319825567. doi: 10.1177/2040622319825567.
    1. Hohmann E., Tetsworth K., Glatt V. Is platelet-rich plasma effective for the treatment of knee osteoarthritis? A systematic review and meta-analysis of level 1 and 2 randomized controlled trials. Eur. J. Orthop. Surg. Traumatol. 2020;30:955–967. doi: 10.1007/s00590-020-02623-4.
    1. Altman R., Asch E., Bloch D., Bole G., Borenstein D., Brandt K., Christy W., Cooke T.D., Greenwald R., Hochberg M., et al. Development of criteria for the classification and reporting of osteoarthritis: Classification of osteoarthritis of the knee. Arthritis Rheum. 1986;29:1039–1049. doi: 10.1002/art.1780290816.
    1. Bellamy N., Buchanan W.W., Goldsmith C.H., Campbell J., Stitt L.W. Validation study of WOMAC: A health status in-strument for measuring clinically important patient relevant outcomes to antirheumatic drug therapy in patients with osteo-arthritis of the hip or knee. J. Rheumatol. 1988;15:1833–1840.
    1. Boonstra A.M., Preuper H.R.S., Reneman M.F., Posthumus J.B., Stewart R.E. Reliability and validity of the visual analogue scale for disability in patients with chronic musculoskeletal pain. Int. J. Rehabil. Res. 2008;31:165–169. doi: 10.1097/MRR.0b013e3282fc0f93.
    1. 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;91:411–417. doi: 10.1097/PHM.0b013e3182aab72.
    1. Primorac D., Molnar V., Rod E., Jeleč Ž., Čukelj F., Matišić V., Vrdoljak T., Hudetz D., Hajsok H., Borić I. Knee Osteoarthritis: A Review of Pathogenesis and State-Of-The-Art Non-Operative Therapeutic Considerations. Genes. 2020;11:854. doi: 10.3390/genes11080854.
    1. Bauer D., Hunter D., Abramson S., Attur M., Corr M., Felson D., Heinegård D., Jordan J., Kepler T., Lane N., et al. Classification of osteoarthritis biomarkers: A proposed approach. Osteoarthr. Cartil. 2006;14:723–727. doi: 10.1016/j.joca.2006.04.001.
    1. Kumavat R., Kumar V., Malhotra R., Pandit H., Jones E., Ponchel F., Biswas S. Biomarkers of Joint Damage in Osteoarthritis: Current Status and Future Directions. Mediat. Inflamm. 2021;2021:5574582. doi: 10.1155/2021/5574582.
    1. Mariani E., Canella V., Cattini L., Kon E., Marcacci M., Di Matteo B., Pulsatelli L., Filardo G. Leukocyte-Rich Plate-let-Rich Plasma Injections Do Not Up-Modulate Intra-Articular Pro-Inflammatory Cytokines in the Osteoarthritic Knee. PLoS ONE. 2016;11:e0156137. doi: 10.1371/journal.pone.0156137.
    1. Fawzy R.M., Hashaad N.I., Mansour A.I. Decrease of serum biomarker of type II Collagen degradation (Coll2-1) by intra-articular injection of an autologous plasma-rich-platelet in patients with unilateral primary knee osteoarthritis. Eur. J. Rheumatol. 2017;4:93–97. doi: 10.5152/eurjrheum.2017.160076.
    1. Kuculmez O., Sirin F.B., Sarikaya N.O., Kocyigi H. Effect of platelet-rich plasma on serum and urine biomarkers in patients with knee osteoarthritis. Int. J. Clin. Exp. Med. 2020;13:5040–5049.
    1. Lychagin A., Lipina M., Garkavi A., Islaieh O., Timashev P., Ashmore K., Kon E. Intraosseous injections of platelet rich plasma for knee bone marrow lesions treatment: One year follow-up. Int. Orthop. 2021;45:355–363. doi: 10.1007/s00264-020-04546-5.
    1. Henrotin Y., Chevalier X., Deberg M., Balblanc J., Richette P., Mulleman D., Maillet B., Rannou F., Piroth C., Mathieu P., et al. Early decrease of serum biomarkers of type II collagen degradation (Coll2-1) and joint inflammation (Coll2-1 NO2) by hyaluronic acid intra-articular injections in patients with knee osteoarthritis: A research study part of the Biovisco study. J. Orthop. Res. 2013;31:901–907. doi: 10.1002/jor.22297.
    1. Riegger J., Rehm M., Büchele G., Brenner H., Günther K.-P., Rothenbacher D., Brenner R.E. Serum Cartilage Oligomeric Matrix Protein in Late-Stage Osteoarthritis: Association with Clinical Features, Renal Function, and Cardiovascular Biomarkers. J. Clin. Med. 2020;9:268. doi: 10.3390/jcm9010268.
    1. Bi X. Correlation of serum cartilage oligomeric matrix protein with knee osteoarthritis diagnosis: A meta-analysis. J. Orthop. Surg. Res. 2018;13:262. doi: 10.1186/s13018-018-0959-y.
    1. Yin W., Liu Y., Hou R., Yin R. Correlation of Bone Morphogenetic Protein-2 Levels in Serum and Synovial Fluid with Disease Severity of Knee Osteoarthritis. Med. Sci. Monit. 2015;21:363–370. doi: 10.12659/MSM.892160.
    1. Davidson E.N.B., Vitters E.L., Van Lent P.L., Van De Loo F.A., Berg W.B.V.D., Van Der Kraan P.M. Elevated extracellular matrix production and degradation upon bone morphogenetic protein-2 (BMP-2) stimulation point toward a role for BMP-2 in cartilage repair and remodeling. Arthritis Res. Ther. 2007;9:R102. doi: 10.1186/ar2305.
    1. Michaud M., Balardy L., Moulis G., Gaudin C., Peyrot C., Vellas B., Cesari M., Nourhashemi F. Proinflammatory Cytokines, Aging, and Age-Related Diseases. J. Am. Med. Dir. Assoc. 2013;14:877–882. doi: 10.1016/j.jamda.2013.05.009.

Source: PubMed

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