HGF Mediates the Anti-inflammatory Effects of PRP on Injured Tendons

Abstract

Platelet-rich plasma (PRP) containing hepatocyte growth factor (HGF) and other growth factors are widely used in orthopaedic/sports medicine to repair injured tendons. While PRP treatment is reported to decrease pain in patients with tendon injury, the mechanism of this effect is not clear. Tendon pain is often associated with tendon inflammation, and HGF is known to protect tissues from inflammatory damages. Therefore, we hypothesized that HGF in PRP causes the anti-inflammatory effects. To test this hypothesis, we performed in vitro experiments on rabbit tendon cells and in vivo experiments on a mouse Achilles tendon injury model. We found that addition of PRP or HGF decreased gene expression of COX-1, COX-2, and mPGES-1, induced by the treatment of tendon cells in vitro with IL-1β. Further, the treatment of tendon cell cultures with HGF antibodies reduced the suppressive effects of PRP or HGF on IL-1β-induced COX-1, COX-2, and mPGES-1 gene expressions. Treatment with PRP or HGF almost completely blocked the cellular production of PGE2 and the expression of COX proteins. Finally, injection of PRP or HGF into wounded mouse Achilles tendons in vivo decreased PGE2 production in the tendinous tissues. Injection of platelet-poor plasma (PPP) however, did not reduce PGE2 levels in the wounded tendons, but the injection of HGF antibody inhibited the effects of PRP and HGF. Further, injection of PRP or HGF also decreased COX-1 and COX-2 proteins. These results indicate that PRP exerts anti-inflammatory effects on injured tendons through HGF. This study provides basic scientific evidence to support the use of PRP to treat injured tendons because PRP can reduce inflammation and thereby reduce the associated pain caused by high levels of PGE2.

Influence of Platelets Rich Plasma on Repair of Superficial Digital Flexor Tendon Rupture in Donkeys (An Experimental Study)

“…Therefore, the improvement of scoring and parameter assessment in the present study was attributed to the role of activated intratendinous injection of PRP. Also, Zhang et al [25] hypothesized that PRP having the hepatocyte growth factor (HGF) which was the reason of anti-inflammatory effects responsible for the pain, heat and swelling rescue effect of the PRP. Moreover, the improvement assessment in the present study is attributed to the role of activated intratendinous injection of PRP as proved ultra-sonographically and histopathologically.…”

Can PRP effectively treat injured tendons?

“…Additionally, PRP did not induce non-tenocyte differentiation into chondrocytes, adipocytes, or osteocytes 16 , suggesting that PRP treatment does not increase the risk of nontendinous tissue formation in treated tendons. In the second study 15 , we demonstrated that PRP's anti-inflammatory function is mediated via HGF contained in PRP by suppressing the levels of prostaglandin biosynthetic pathway components (COX-1, COX-2, and mPGES-1 expression) and PGE2 production. These results were corroborated by our animal model studies where PRP injections (which may contain small amounts of leukocytes due to difficulty in removing all these cells from a small volume) reReview article © C I C E d i z i o n i I n t e r n a z i o n a l i duced COX-1 and COX-2 protein expression and lowered PGE2 levels in the wounded Achilles tendons of mice.…”

Effect of plasma rich in growth factors on the early phase of healing of surgically severed Achilles tendon in sheep: histological study

“…It may suggest a role of PRGF on the modulation of the inflammatory phenomenon during the early phase of tendon repair. HGF and TGF-β, growth factors contained in PRGF, have been associated with a significant role in the anti-inflammatory effect in human cartilage and tendon injuries in in vitro experiments (Bendinelli et al 2010;Zhang et al 2013).…”

“…Previous studies have shown the importance of inflammation and angiogenesis modulation in tendon injuries (Dakin et al 2014;Manning et al 2014). The growth factors and other active proteins secreted by platelets play an important role in the modulation of inflammatory response and the induction of a rapid increase in specific cell populations, including endothelial cells, migrating fibroblasts, and resident cells of the tendon (Andia et al 2010;Zhang et al 2013). Some in vitro and in vivo PRP studies reported anti-inflammatory effects mainly explained by the activity of Hepatocyte growth factor (HGF) and transforming growth factor beta 1 (TGF-β1) (Bendinelli et al 2010;Fernandez-Sarmiento et al 2013;Mazzocca et al 2013;Zhang et al 2013).…”