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

In vitro studies indicate that transforming growth factor-beta (TGF-beta) has a role in the regulation of bone cell activities. However, little is known about the effects of TGF-beta on bone when it is administered systemically. This study was undertaken to evaluate the in vivo effects of TGF-beta2 on bone and marrow cells in the ovariectomized rat bone loss model. Female Sprague-Dawley rats, aged 95 days, were divided into 4 groups. Group 1 was sham operated: groups 2-4 were ovariectomized. Groups 3 and 4 received daily injections of 10 mug and 50 mug of TGF-beta2/kg body weight, respectively. Groups 1 and 2 received the solvent vehicle. All animals were sacrificed after 35 days. Ovariectomy caused a significant increase in, total mononuclear marrow cells, the number of TRAP positive multinucleated cells formed in culture of marrow cells, and the number of trabecular osteoclasts and osteoblasts. These increases were associated with loss of cancellous bone in the proximal tibia. TGF-beta2 completely prevented the increase in the number of TRAP positive multinucleated cells, and caused a small but not statistically significant decrease in the number of trabecular osteoclasts. However, TGF-beta2 had no significant effect on the number of total mononuclear marrow cells and on the loss of cancellous bone due to ovariectomy. We conclude that TGF-beta2 probably plays a role in the regulation of the proliferation of osteoclast progenitors in bone marrow in vivo. Studies carried out over a longer period are required to determine whether it will modulate the increase in osteoclast and osteoblast numbers that occur in cancellous bone following ovariectomy.