Simvastatin With PRP Promotes Chondrogenesis of Bone Marrow Stem Cells In Vitro and Wounded Rat Achilles Tendon–Bone Interface Healing In Vivo

Abstract

Background: Tendons and ligaments are joined to bone in a specialized interface that transmits force from muscle to bone and permits body movement. Tendon/ligament injuries always occur in the interface areas, and injured tendons/ligaments have a limited healing response because the insertion site is composed of a fibrocartilaginous zone. Purpose: To study the effect of simvastatin with platelet-rich plasma (PRP) on chondrogenesis of rat bone marrow stem cells (BMSCs) in vitro and wounded rat Achilles tendon–bone interface healing in vivo. Study Design: Controlled laboratory study. Methods: The in vitro model was performed by the culture of rat BMSCs with various concentrations of simvastatin (0, 10, 50, 100 nM) for 2 weeks. The effect of simvastatin on the chondrogenic differentiation of the BMSCs was examined by histochemical analysis and real-time quantitative reverse transcription polymerase chain reaction. The in vivo model was carried out by testing the healing effect of simvastatin with PRP on 12 wounded rat Achilles tendon–bone interfaces. Results: Simvastatin induced chondrogenic differentiation of rat BMSCs in a concentration-dependent manner as evidenced by histological staining and real-time quantitative reverse transcription polymerase chain reaction. The wounds treated with simvastatin alone or with simvastatin-containing PRP gel healed much faster than the wounds treated with saline alone or PRP alone. Histological analysis showed that higher percentages of healed tissues were positively stained with safranin O and fast green in wounds treated with simvastatin-containing PRP gel than in the other 3 groups. Immunohistochemical analysis further demonstrated these findings, as evidenced by more positively stained healed tissues with collagen I and II antibodies in the wound areas treated with simvastatin-containing PRP gel than the other 3 groups. Conclusion: The combination of simvastatin with PRP induced chondrogenesis of BMSCs in vitro and enhanced fibrocartilage formation in vivo. The simvastatin–PRP gel treatment promotes wounded tendon-bone interface healing in clinical treatment. Clinical Relevance: The combination of simvastatin with PRP may be a good clinical treatment for wounded tendon/ligament junction healing, especially for acute sports-related tendon/ligament injuries.