ISSN: 2577-297X
Authors: Kostenuik PJ*, Mirza FS and Collins M
Platelet-rich plasma (PRP) is a popular autologous therapy in the tissue regenerative technology space based on its enriched milieu of platelet-released growth factors (GFs), including platelet-derived growth factor (PDGF) and vascular endothelial growth factor (VEGF). PRP is frequently used for hair restoration, wound healing, tendon and ligament repairs, and other soft-tissue settings, but PRP did not fulfill its original promise for enhancing bone grafts and bone augmentation in dentistry or orthopedics because it does not consistently promote osteogenesis. The effects of PRP on bone regeneration are often described as controversial, contradictory, and confusing, including evidence that greater platelet enrichment often leads to lesser osteogenic responses. The latter paradox suggests that limited PRP efficacy in bone regeneration may relate to platelet-derived factors that inhibit osteoblasts rather than inadequate GF concentrations. One candidate platelet-derived anti-osteogenic factor is Dickkopf-1 (DKK1), a potent soluble inhibitor of Wnt signaling that limits bone regeneration after bone damage. Recognizing that platelets store DKK1 in their alpha granules and rapidly release it upon platelet activation, we evaluated levels of DKK1, PDGF, and VEGF in human serum, plasma, platelet-poor plasma (PPP), and PRP. Sclerostin, another inhibitor of Wnt signaling that limits bone formation in undamaged bone, was also evaluated because platelets are not known to secrete sclerostin. We show that DKK1, PDGF, and VEGF concentrations are much higher in serum versus plasma, probably due to platelet activation during serum preparation. DKK1, PDGF, and VEGF concentrations were also higher in PRP versus plasma, and in plasma versus PPP. Activation of plasma or PRP with thrombin resulted in marked increases in DKK1, PDGF, and VEGF concentrations, with DKK1 levels in activated PRP being over 40-fold higher than the minimum concentration reported to inhibit osteogenesis in cell culture models. Conversely, sclerostin levels in plasma and PRP were unaffected by platelet activation and were significantly lower in serum versus standard plasma, providing new evidence that platelets do not secrete sclerostin. These results suggest that the beneficial effects of high GF levels in PRP may be limited by the presence of high levels of DKK1 released from the same platelet alpha granules.
Keywords: Platelet-Rich Plasma; DKK1; Wnt Signaling; Bone Regeneration; Hair Growth
