Randomized, Placebo‐Controlled Analysis of the Knee Synovial Environment Following Platelet‐Rich Plasma Treatment for Knee Osteoarthritis

Abstract

Background Platelet‐rich‐plasma (PRP) is used to treat knee osteoarthritis; however, mechanistic evidence of PRP effectiveness for pain relief is limited. Objective To assess molecular biomarkers and mesenchymal stem cells (MSCs) in synovial fluid during PRP treatment of the osteoarthritic knee joint. Design Single blinded, randomized, placebo controlled pilot study. Setting Veterans Affairs Medical Center. Participants Seventeen participants with mild to moderate knee osteoarthritis were randomized in a 2:1 placebo‐controlled ratio, receiving PRP or saline (placebo) intra‐articular injection into the knee joint. Methods Knee synovial fluid was analyzed before the respective injections and again 10 days following injection. Participants were followed up to 12 months completing visual analog scale (VAS) and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) questionnaires at intervals over that period. Main Outcome Measures The effects of PRP on synovial protein and MSC gene expression levels were measured by multiplex enzyme‐linked immunosorbent assay and quantitative polymerase chain reaction. Results Novel biomarkers including levels of interleukin (IL)‐5, IL‐6, IL‐10, and tumor necrosis factor‐α were measured in synovial fluid 10 days after PRP treatment. Altered gene expression profiles in MSCs from patients treated with PRP were observed for matrix metalloproteinases and inflammatory markers (IL‐6, IL‐8, CCL2, TNF‐α). A2M protease was significantly increased following PRP treatment (P = .005). WOMAC scores declined for up to 3 months from baseline levels and remained low at 6 and 12 months in the PRP group. In contrast, WOMAC scores for patients receiving the saline injection were relatively unchanged for up to 12 months. Conclusions We report significant changes for the biomarker A2M (P = .005) as well as differences in expression of cellular markers and postulate that PRP modulates the local knee synovial environment by altering the inflammatory milieu, matrix degradation, and angiogenic growth factors. The PRP treatment group had less pain and stiffness and improved function scores.

Intra-Articular Platelet-Rich Plasma Injections in Knee Osteoarthritis: A Review of Their Current Molecular Mechanisms of Action and Their Degree of Efficacy

“…Tucker et al postulated that PRP modulates the local knee synovial environment by modifying the inflammatory milieu, matrix degradation, and angiogenic growth factors. The group receiving PRP had less pain and stiffness and improved function scores [37].…”

“…In a single-blinded, randomized, placebo-controlled pilot study, Tucker et al assessed molecular biomarkers and mesenchymal stem cells in synovial fluid during PRP treatment of the osteoarthritic knee joint [37]. Seventeen patients with mild-to-moderate knee OA were randomized in a 2:1 placebo-controlled ratio, receiving PRP or saline (placebo) intraarticular injection of the knee.…”

“…In patients with knee OA, LR-PRP demonstrated effectiveness in meaningful end points for functional and patient-reported outcomes at early time points [51]. Table 2 summarizes the efficacy of intra-articular PRP injections in knee OA [37][38][39][40][41][42][43][44][45][46][47][48][49][50][51].…”

Role of Platelets in Osteoarthritis—Updated Systematic Review and Meta-Analysis on the Role of Platelet-Rich Plasma in Osteoarthritis

“…Thirty-seven studies compared PRP versus control groups [ 88 , 97 , 98 , 99 , 100 , 101 , 102 , 103 , 104 , 105 , 106 , 107 , 108 , 109 , 110 , 111 , 112 , 113 , 114 , 115 , 116 , 117 , 118 , 119 , 120 , 121 , 122 , 123 , 124 , 125 , 126 , 127 , 128 , 129 , 130 , 131 , 132 ], six studies compared PRP with the addition of another substance (MSC or HA) versus control groups [ 122 , 123 , 133 , 134 , 135 ], six studies compared multiple injections of PRP [ 100 , 118 , 119 , 136 , 137 , 138 ], five studies compared PRGF-Endoret versus control groups [ 125 , 128 , 139 , 140 , 141 ], two studies compared autologous conditioned plasma (ACP) versus control groups […”

The biology of mesenchymal stem/stromal cells in the treatment of osteoarthritis

“…At present, OA is generally managed through the use of pain control for a decade or more, 131 until end-stage disease, when arthroplasty is usually the most effective choice. 7,[132][133][134][135] However there are also a range of options for intra-articular administration of therapeutics to control flare-ups in pain in single joints, including corticosteroids (CS) 136 , HA 137 and Platelet-Rich Plasma (PRP) 138,139 , some of which may also have disease-modifying activity. 8,[140][141][142] MSCs and disease-modifying biologicals such as PRP are likely to act through similar mechanisms, involving the activation and inhibition of cytokine and growth factor networks in the joints 143 and some evidence has also been provided to suggest that PRP implanted into cartilage lesions may recruit chondro-progenitor cells.…”