One day exposure to FGF-2 was sufficient for the regenerative repair of full-thickness defects of articular cartilage in rabbits

Abstract

Administration of fibroblast growth factor (FGF)-2 for 2 weeks induces a successful cartilaginous repair response in 5-mm full-thickness articular cartilage defects in rabbits. The purpose of this study was to investigate the effects of a short time exposure to FGF-2 on the repair of the defects. Five-mm-diameter cylindrical defects, which do not repair spontaneously, were created in the femoral trochlea of the rabbit knees. The defects were administered sterile saline or FGF-2 (150pg/h) via an osmotic pump for the initial 1 day, 3 days, or 2 weeks, and we assessed the FGF-2 action on the proliferation and migration of mesenchymal cells in the reparative tissue. Using a total of 126 rabbits, we performed three sets of experiments. We also studied the effect of FGF-2 on migration of marrow-derived mesenchymal cells in vitro. FGF-2 treatment for 1 day or 3 days induced the sequential chondrogenic repair responses that led to successful cartilaginous resurfacing of defects within 8 weeks as well as the 2-week treatment did. We confirmed by a radioisotope study that FGF-2 injected was rapidly eliminated from the defects (a residual ratio of 50% within 30min). The effect of FGF-2 on cultured marrow-derived cells suggested that FGF-2 facilitated the mobilization and migration of replicating mesenchymal cells from bone marrow. Only 1 day exposure to FGF-2 is sufficient for induction of the chondrogenic repair response in 5-mm-diameter full-thickness defects of articular cartilage in rabbits. FGF-2 stimulated the recruitment of mesenchymal cells into the defects, which was a limiting step for the induction of cartilage.