Dual Effect of Platelet Lysate on Human Articular Cartilage: A Maintenance of Chondrogenic Potential and a Transient Proinflammatory Activity Followed by an Inflammation Resolution

Abstract

Platelet-rich plasma (PRP), a cocktail of platelet growth factors and bioactive proteins, has been proposed as a therapeutic agent to restore damaged articular cartilage. We report the biological effect of the platelet lysate (PL), a PRP derivative, on primary human articular chondrocytes cultured under both physiological and inflammatory conditions. When added to the culture medium, PL induced a strong mitogenic response in the chondrocytes. The in vitro expanded cell population maintained a chondrogenic redifferentiation potential as revealed by micromass culture in vitro and ectopic cartilage formation in vivo. Further, in chondrocytes cultured in the presence of the proinflammatory cytokine interleukin-1α (IL-1α), the PL induced a drastic enhancement of the synthesis of the cytokines IL-6 and IL-8 and of neutrophil-gelatinase associated lipocalin, a lipocalin expressed during chondrocyte differentiation and inflammation. These events were mediated by the p38 MAP kinase and NF-κB pathways. We observed that inflammatory stimuli activated phospo-MAP kinase-activated protein kinase 2, a direct target of p38. The proinflammatory effect of the PL was a transient phenomenon; after an initial upregulation, we observed significant reduction of the NF-κB activity together with the repression of the inflammatory enzyme cyclooxygenase-2. Moreover, the medium of chondrocytes cultured in the simultaneous presence of PL and IL-1α, showed a significant enhancement of the chemoattractant activity versus untreated chondrocytes. Our findings support the concept that the platelet products have a direct beneficial effect on articular chondrocytes and could drive in sequence a transient activation and the resolution of the inflammatory process, thus providing a rational for their use as therapeutic agents in cartilage inflammation and damage.

Anti-Inflammatory Strategies in Cartilage Repair

“…24 Paradoxically, platelet lysate (PL), a PRP derivative, was thought to play a role as a proinflammatory agent, acting synergistically with the canonical proinflammatory cytokines such as IL-1a, thus enhancing the initial inflammatory response; surprisingly, PL also contributes to the downregulation of the NF-kB signal pathway and cyclooxygenase 2 (COX-2) expression, thus triggering the resolution of the inflammation. 25 The anti-inflammatory role of PRP was also demonstrated in an in vivo study. In the antigen-induced arthritis porcine model, the intra-articular injection of PRP attenuated the subsequent inflammatory response.…”

Platelet-Rich Plasma Inhibits Mechanically Induced Injury in Chondrocytes

“…It was reported that IL-6 and IL-8 gene expression were significantly higher in chondrocytes exposed to 16 hours' incubation with IL1a and platelet lysate compared with IL-1a alone, indicating the proinflammatory actions of platelet lysate. 26 However, after 40 hours' incubation, COX-2 gene expression was significantly reduced compared with the IL-1a group alone, indicating the resolution of inflammation after longer exposure to PRP. 26 These observations are consistent with our finding that 72 hours' incubation with PRP in the early-PRP group resulted in down-regulation of CTS-induced MMP-3, iNOS, and COX-2 genes whereas 48 hours' incubation in the mid-PRP group induced down-regulation only of MMP-3 and 24 hours' incubation in the late-PRP group led to increased MMP-13 expression.…”

Evaluation of intra-articular injection of autologous platelet lysate (PL) in horses with osteoarthritis of the distal interphalangeal joint

“…In addition, Anitua et al (2007) found that platelet-released growth factors enhanced hyaluronic acid secretion and might be useful in joint homeostasis. Platelet lysate (PL), among other autologous platelet-derived preparations as sources of growth factors and cytokines, has been evaluated for its usefulness in bone and cartilage engineering, mainly in humans, in vitro and in clinical studies (Zaky et al 2008;Pereira et al 2013;Ruggiu et al 2013;Zhu et al 2013;Xie et al 2014).…”