Wnt5a/Platelet-rich plasma synergistically inhibits IL-1β-induced inflammatory activity through NF-κB signaling pathway and prevents cartilage damage and promotes meniscus regeneration.

Abstract

Noncanonical Wnt5a is a particularly attractive growth factor to maintain chondrogenesis. Platelet-rich plasma (PRP) is an autologous blood-derived product and a source of bioactive growth factors involved in tissue regeneration. The present study aimed to investigate the effect and inflammation reaction of Wnt5a/PRP on meniscus cells, and evaluate meniscus regeneration and osteoarthritis (OA) prevention by the application of Wnt5a/PRP gel in a rabbit model of massive meniscal defect. In vitro, the proliferation, migration, differentiation, and interleukin-1 beta (IL-1β) IL-1β-induced inflammation reaction of meniscus cells treated by Wnt5a and PRP was assessed. In vivo, the anterior half of the medial meniscus of 18 New Zealand rabbits was excised and implanted with PRP gel, Wnt5a/PRP gel or untreated. After 6 and 12weeks, the regenerated meniscus were evaluated. Wnt5a can promote the migration of meniscus cells. PRP and Wnt5a had synergistic effect in promoting the proliferation and chondrogenic differentiation of meniscus cells. The IL-1β-induced meniscus cells study showed that PRP and Wnt5a had the anti-inflammatory actions through nuclear factor kB (NF-κB) signaling pathway. PRP and Wnt5a/PRP significantly inhibited the increase of the p-p65/p65 and p-IκB-α/IκB-α ratios. In vivo transplantation of Wnt5a/PRP gel was demonstrated to promote meniscus regeneration, while reducing OA of knee joint. Wnt5a with PRP had the anti-inflammatory activity in an IL-1β-induced inflammatory model. They can synergistically improve the chondorgenic differentiation of meniscus cells. Wnt5a/PRP gel treatment could potentially be developed into a new method for meniscus regeneration and the prevention of OA.