Molecular basis of anti‐inflammatory action of platelet‐rich plasma on human chondrocytes: Mechanisms of NF‐κB inhibition via HGF

Abstract

Loss of articular cartilage through injury or disease presents major clinical challenges also because cartilage has very poor regenerative capacity, giving rise to the development of biological approaches. As autologous blood product, platelet-rich plasma (PRP) provides a promising alternative to surgery by promoting safe and natural healing. Here we tested the possibility that PRP might be effective as an anti-inflammatory agent, providing an attractive basis for regeneration of articular cartilage, and two principal observations were done. First, activated PRP in chondrocytes reduced the transactivating activity of NF-kB, critical regulator of the inflammatory process, and decreased the expression of COX2 and CXCR4 target genes. By analyzing a panel of cytokines with different biological significance, in activated PRP we observed increases in hepatocyte growth factor (HGF), interleukin-4 and tumor necrosis factor-α (TNF-α). HGF and TNF-α, by disrupting NF-kB-transactivating activity, were important for the anti-inflammatory function of activated PRP. The key molecular mechanisms involved in PRP-inhibitory effects on NF-kB activity were for HGF the enhanced cellular IkBα expression, that contributed to NF-kB-p65 subunit retention in the cytosol and nucleo-cytoplasmic shuttling, and for TNF-α the p50/50 DNA-binding causing inhibition of target-gene expression. Second, activated PRP in U937-monocytic cells reduced chemotaxis by inhibiting chemokine transactivation and CXCR4-receptor expression, thus possibly controlling local inflammation in cartilage. In conclusion, activated PRP is a promising biological therapeutic agent, as a scaffold in micro-invasive articular cartilage regeneration, not only for its content of proliferative/differentiative growth factors, but also for the presence of anti-inflammatory agents including HGF.

PRP for Degenerative Cartilage Disease: A Systematic Review of Clinical Studies

“…Other basic science research demonstrated that PRP causes inhibition of the transactivating activity of nuclear factor-κB (NF-κB) and decreased expression of cyclooxygenase-2, which are important inflammatory regulators. 13 These findings suggest that PRP has the ability to stimulate local host cartilage and improve repair. Anitua et al examined the effect of a platelet-derived preparation rich in growth factors (PRGFs) in OA synovial cell biology and revealed the ability of PRGF to stimulate HA synthesis, driving the secretion of HA by the synovial fibroblasts.…”

The P makes the difference in plasma rich in growth factors (PRGF) technology

“…It also stimulates the proliferation and chondrogenic [11], adipogenic and myogenic differentiation of mesenchymal stem cells, also promotes neuronal differentiation [12] and induces a chemotactic effect on vascular endothelial cells. In addition, it has also been demonstrated that hepatocyte growth factor (HGF), mainly present in the plasma, stimulates cell proliferation [13] and migration while inhibits NF-B, a key nuclear factor implicated in inflammatory responses [14]. It is also remarkable the influence of HGF as an antifibrotic mediator [15,16].…”

Initial Experience of Face Augmentation Using Fat Graft-Platlet Rich Plasma Mix

“…In addition, Kakudo et al showed that activated platelet-rich plasma contains large amounts of PDGF-AB and TGF-β1 that promote the proliferation of human adipose-derived stem cells and human dermal fibroblast in vitro [32]. Lastly, Bendinelli et al reported the anti-inflammatory effect of PRP by a reduction of COX2 and CXCR4 gene expression [33].…”