Transforming growth factor β1 stimulates bone formation and resorption in an in-vivo model in rabbits

The influence of TGFβ1 on bone was studied in a titanium device implanted into the tibia of rabbits. TGFβ1 was infused via an Alzet osmotic pump calibrated to deliver at a rated of 200ng daily for 2 weeks before replacement. A hollow channel is incorporated into the device into which tissue can grow, and the histological sequence of events was observed over 6 weeks. In control samples, the rod-shaped piece of tissue at 2W consisted of spindle-shaped cells in the center, flanked at both ends by islands of trabecular bone lined by cuboidal osteoblasts and osteoclasts. By 4W, ingrowth of bone reached the center if the specimen, by which time, the bone surfaces were opposed by a single layer of flattened osteoblasts. However, osteoclastic resorption continued unabated so that by 6W, only a thin layer of cortical bone remained, enclosing a marrow cavity with hemopoietic elements. Significant differences were observed in samples continuously infused with TGFβ1. At 2W, trabecular bone had reached further towards the center of the specimen and the granulation tissue was made up of cells that were more plump and cuboidal compared to the spindle cells of control sample. At 3W, there was increased bone volume and osteoid seams were thicker, covering a greater extent of the trabeculae surfaces. At 4W, the bony trabeculae were up to 3 times thicker than control trabeculae. There was very active bone resorption with many multinucleate osteoclasts and multilayered aggregates of cuboidal osteoblasts lining bony surfaces. Yet at 6W, the morphological appearance was similar to control samples. This implies that even with continued infusion of TGFβ1, bone resorption was the dominant activity during the last 2 weeks. The results are consistent with a significant effect of TGFβ1 on bone formation followed by a wave of increased bone resorption.