TRANSFORMING GROWTH-FACTOR-BETA-1 STIMULATES BONE-FORMATION AND RESORPTION IN AN IN-VIVO MODEL IN RABBITS

The influence of TGF beta(1) on bone was studied in a titanium device implanted into the tibia of rabbits. TGF beta(1) was infused via an Al zet osmotic pump calibrated to deliver at a rated of 200ng daily for 2 weeks before replacement. A hollow channel is incorporated into the d evice into which tissue can grow, and the histological sequence of eve nts was observed over 6 weeks. In control samples, the rod-shaped piec e of tissue at 2W consisted of spindle-shaped cells in the center, fla nked at both ends by islands of trabecular bone lined by cuboidal oste oblasts and osteoclasts. By 4W, ingrowth of bone reached the center if the specimen, by which time, the bone surfaces were apposed by a sing le layer of flattened osteoblasts. However, osteoclastic resorption co ntinued unabated so that by 6W, only a thin layer of cortical bone rem ained, enclosing a marrow cavity with hemopoietic elements. Significan t differences were observed in samples continuously infused with TGF b eta(1). At 2W, trabecular bone had reached further towards the center of the specimen and the granulation tissue was made up of cells that w ere more plump and cuboidal compared to the spindle cells of control s ample. At 3W, there was increased bone volume and osteoid seams were t hicker, covering a greater extent of the trabeculae surfaces. At 4W, t he bony trabeculae were up to 3 times thicker than control trabeculae. There was very active bone resorption with many multinucleate osteocl asts and multilayered aggregates of cuboidal osteoblasts lining bony s urfaces. Yet at 6W, the morphological appearance was similar to contro l samples. This implies that even with continued infusion of TGF beta( 1), bone resorption was the dominant activity during the last 2 weeks. The results are consistent with a significant effect of TGF beta(1) o n bone formation followed by a wave of increased bone resorption.