SYSTEMIC ADMINISTRATION OF RECOMBINANT TRANSFORMING GROWTH-FACTOR-BETA-2 (RTGF-BETA-2) STIMULATES PARAMETERS OF CANCELLOUS BONE-FORMATION IN JUVENILE AND ADULT-RATS

Transforming growth factor beta is a multifunctional protein with know n actions on bone and bone cells. The ability of TGF-beta to stimulate osteogenic parameters in vitro and osteogenesis adjacent to injection sites in vivo is well established. The purpose of this study was to d etermine if systemic administration of recombinant TGF-beta 2 (rTGF-be ta 2) could stimulate bone formation in rats of different ages. Juveni le (25-day-old) and adult (160-day-old) rats were treated daily for 5 days and 14 days, respectively, with rTGF-beta 2 given by subcutaneous injection. Bone formation was measured in cancellous bone of the lumb ar vertebrae in juvenile rats and the femoral epiphysis in adult rats. Endochondral bone growth rates were measured in the distal femurs fro m both juvenile and adult rats using histomorphometric methods. System ic administration of rTGF-beta 2 resulted in substantial increases in bone formation rates (both surface and volume referent) in both juveni le and adult rats. In the juvenile rats, rTGF-beta 2 increased the per cent double labeled surface and the mineral appositional rate. In the adult rats, TGF-beta 2 treatment increased the double labeled surface and also endochondral (longitudinal) growth parameters without changin g the number of osteoclasts or the number of osteoclast nuclei per cel l. These results demonstrate that short-term systemic administration o f rTGF-beta 2 substantially increases cancellous bone formation rate i n rats.