IN-VIVO EFFECTS OF TRANSFORMING GROWTH-FACTOR-BETA-2 IN OVARIECTOMIZED RATS

In vitro studies indicate that transforming growth factor-beta (TGF-be ta) has a role in the regulation of bone cell activities. However, lit tle is known about the effects of TGF-beta on bone when it is administ ered systemically. This study was undertaken to evaluate the in vivo e ffects of TGF-beta2 on bone and marrow cells in the ovariectomized rat bone loss model. Female Sprague-Dawley rats, aged 95 days, were divid ed into 4 groups. Group 1 was sham operated: groups 2-4 were ovariecto mized. Groups 3 and 4 received daily injections of 10 mug and 50 mug o f TGF-beta2/kg body weight, respectively. Groups 1 and 2 received the solvent vehicle. All animals were sacrificed after 35 days. Ovariectom y caused a significant increase in, total mononuclear marrow cells, th e number of TRAP positive multinucleated cells formed in culture of ma rrow cells, and the number of trabecular osteoclasts and osteoblasts. These increases were associated with loss of cancellous bone in the pr oximal tibia. TGF-beta2 completely prevented the increase in the numbe r of TRAP positive multinucleated cells, and caused a small but not st atistically significant decrease in the number of trabecular osteoclas ts. However, TGF-beta2 had no significant effect on the number of tota l mononuclear marrow cells and on the loss of cancellous bone due to o variectomy. We conclude that TGF-beta2 probably plays a role in the re gulation of the proliferation of osteoclast progenitors in bone marrow in vivo. Studies carried out over a longer period are required to det ermine whether it will modulate the increase in osteoclast and osteobl ast numbers that occur in cancellous bone following ovariectomy.