Hyperuricemic PRP in Tendon Cells

Abstract

Platelet-rich plasma (PRP) is injected within tendons to stimulate healing. Metabolic alterations such as the metabolic syndrome, diabetes, or hyperuricemia could hinder the therapeutic effect of PRP. We hypothesise that tendon cells sense high levels of uric acid and this could modify their response to PRP. Tendon cells were treated with allogeneic PRPs for 96 hours. Hyperuricemic PRP did not hinder the proliferative actions of PRP. The gene expression pattern of inflammatory molecules in response to PRP showed absence of IL-1b and COX1 and modest expression of IL6, IL8, COX2, and TGF-b1. IL8 and IL6 proteins were secreted by tendon cells treated with PRP. The synthesis of IL6 and IL8 proteins induced by PRP is decreased significantly in the presence of hyperuricemia (P = 0.017 and P = 0.012, resp.). Concerning extracellular matrix, PRP-treated tendon cells displayed high type-1 collagen, moderate type-3 collagen, decorin, and hyaluronan synthase-2 expression and modest expression of scleraxis. Hyperuricemia modified the expression pattern of extracellular matrix proteins, upregulating COL1 (P = 0.036) and COMP (P = 0.012) and downregulating HAS2 (P = 0.012). Positive correlations between TGF-b1 and type-1 collagen (R = 0.905, P = 0.002) and aggrecan (R = 0.833, P = 0.010) and negative correlations between TGF-b1 and IL6 synthesis (R = −0.857, P = 0.007) and COX2 (R = −0.810, P = 0.015) were found.

Angiogenic and innate immune responses triggered by PRP in tendon cells are not modified by hyperuricemia

“…A possible source of increased serum MCP-1 includes not only circulating monocytes and macrophages but also local cells such as tenocytes. Notwithstanding in our cell culture model, hyperuricemia is a minor stressor for tenocytes that does not induce changes in MCP-1 but in the synthesis of IL-8 confirming a previous study 6 . However, we cannot rule out that hyperuricemia could modify the polarization of infiltrating monocytes/macrophages 18 .…”

“…However, hyperuricemia is a nondramatic alteration of tissue homeostasis, in contrast to the more substantial alteration provoked when uric acid condensates, and forms monosodium urate (MSU) crystals, the hallmark of gout. Recently, we have shown that high concentrations of uric acid in the tendon cell microenvironment involve a mild alteration in extracellular matrix homeostasis in the context of platelet rich plasma (PRP) 6 . PRP is a plasma preparation, obtained from autologous peripheral blood that contains a platelet level above peripheral blood and, as often found in tendon treatment, it can hold a high concentration of leukocytes (L-PRP) 7,8 .…”

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

“…Samples were obtained after receiving informed consent from patients and local ethics committee approval. Tendon cells were isolated by an explant procedure and cultured as previously described [9]. All the experiments were performed in cells at passages between two and three, ie, to avoid dedifferentiation no more than three times the cells in the culture have been split and subcultured.…”

Current Concepts and Translational Uses of Platelet Rich Plasma Biotechnology

“…In addition, PRP releases a known chemotactic cytokine for neutrophils, CXCL8/IL8. Moreover, we have recently shown that these chemotactic signals are reinforced and augmented by local cell synthesis in vitro [13]. PRP can also modify the lifespan of infiltrated leukocytes by modifying the molecular environment of the injury.…”