Bone morphogenetic protein 2 improves patellar tendon healing by promoting migration and proliferation of tenocytes

The repair of injured tendons remains a great challenge because of the poor intrinsic healing capacity of tendons. In this study, we examined the spatiotemporal expression pattern of the bone morphogenetic protein 2 (bmp-2) gene in normal and experimentally injured rat patellar tendons. We also investigated the ability of exogenously applied BMP-2 to promote patellar tendon healing. In situ hybridization with bmp-2 and alk-6 (bmp-2 receptor) antisense riboprobes revealed that both genes were normally expressed at low levels in intact rat tendons. However, bmp-2 expression was significantly upregulated in tenocytes found in the wound site at 7 d and later following tendon injury. In addition, it was found that bmp-2 was expressed in cultured patellar tenocytes. Application of exogenous BMP-2 to the tendon wound site significantly enhanced tendon repair. Moreover, in vitro and in vivo studies further demonstrated that BMP-2 enhanced tenocyte proliferation and migration to the wound site. The detectable amount of BMP-2 in normal tendons suggests that a basal level of bmp-2 expression was likely present to maintain the normal functions of the patellar tendon. Injury to the tendon induced increased bmp-2 expression intrinsically, but the expression level was insufficient for proper tendon repair. Our findings indicate that it is possible to significantly improve tendon healing by applying exogenous BMP-2 to the wound site, inferring that this protein could be developed as a potential therapeutic reagent for the treatment of damaged tendons.