Platelet-rich Plasma Modulates the Secretion of Inflammatory/Angiogenic Proteins by Inflamed Tenocytes

Abstract

Background: Platelet-rich plasma therapies for tendinopathy appear to provide moderate pain reduction. However, the biological mechanisms behind the observed clinical effects remain poorly characterized. Questions/purposes: The purpose of this study was to explore whether platelet-rich plasma modifies the inflammatory/angiogenic status of already inflamed tenocytes by examining (1) gene expression; (2) modulation of chemokine and interleukin secretion; and (3) differences between healthy and tendinopathic tenocytes. Methods: Cells from both healthy and tendinopathic tendons were exposed to interleukin (IL)-1ß and after treated with platelet-rich plasma. Modifications in the expression of selected genes were assessed by real-time reverse transcription-polymerase chain reaction and changes in secretion of angiogenic/inflammatory molecules by enzyme-linked immunosorbent assay. Platelet-rich plasma-induced changes in tendinopathic cells were compared with normal after normalizing platelet-rich plasma data against IL-1ß status in each specific sample. Results: In IL-1ß-exposed cells, platelet-rich plasma downregulates expression of IL-6/CXCL-6 (mean, 0.015; 95% confidence interval [CI], 0.005–0.025; p = 0.026), IL-6R (mean, 0.61; 95% CI, 0.27–0.95; p = 0.029), and IL-8/CXCL-8 (mean, 0.02; 95% CI, 0.007–0.023; p = 0.026). Secretion of IL-6/CXCL6, 0.35 (95% CI, 0.3–0.4; p = 0.002), IL-8/CXCL8, 0.55 (95% CI, 0.5–0.7; p = 0.01), and monocyte chemoattractant protein-1/CCL2, 0.40 (95% CI, 0.2–0.6; p = 0.001) was reduced by platelet-rich plasma, whereas vascular endothelial growth factor increased by twofold, (95% CI, 1.7–2.3; p < 0.001). RANTES/CCL5 increased by10-fold (95% CI, 4–17) and hepatocyte growth factor by 21-fold (95% CI, 0.2–42) in tendinopathic and by 2.3-fold (95% CI, 2–3) and threefold (95% CI, 1–5) in normal cells (p = 0.005 for both). Conclusions: Platelet-rich plasma induces an immunomodulatory and proangiogenic phenotype consistent with healing mechanisms with few differences between tendinopathic and normal cells. Clinical Relevance: Platelet-rich plasma injections in pathological and nearby tissue might help to recover tendon homeostasis.