SHORT-TERM LOCAL INJECTIONS OF TRANSFORMING GROWTH FACTOR-BETA(1) DECREASE OVARIECTOMY-STIMULATED OSTEOCLASTIC RESORPTION IN-VIVO IN RATS

Estrogen deficiency in rats is responsible for increased osteoclastic resorption and a subsequent rapid bone loss. TGF-beta, which is known to have acute effects on bone resorption in several in vitro models, h as been shown to be secreted by osteoblastic cells in vitro in respons e to 17 beta-estradiol, but little is known about its in vivo effects on bone resorption. We therefore decided to investigate the short-term effect of TGF-beta(1) on bone resorption in ovariectomized rats. TGF- beta(1) (0.04-20 ng/injection), or vehicle, was injected daily directl y into the bone marrow space, through a thin catheter implanted in the distal end of the right femur, during 4 consecutive days, starting 14 days after the ovariectomy. Bone histomorphometry was performed in th e secondary spongiosa of the metaphysis of injected femurs and compare d with vehicle-injected femurs of sham ovariectomized rats. Ovariectom y was associated with a marked increase in the resorption surface, a 2 -fold increase in the number of osteoclasts, and no change in the numb er of TRAP-positive marrow cells distant from bone surfaces. Bone reso rption was significantly lower in the TGF-beta(1)-injected bones of ov ariectomized rats, as compared with vehicle injected bones: the osteoc last surface and the number of osteoclasts were, respectively, 11.0 +/ - 5.1% versus 20.8 +/- 1.3% and 287 +/- 41 versus 505 +/- 53, in bones injected with 0.2 ng of TGF-beta(1) as compared with vehicle-injected bones (mean +/- SE, p < 0.05). The bone formation rate, assessed by d ouble tetracycline labeling, was increased in ovariectomized rats, but was significantly decreased in TGF-beta(1)-injected bones (2 and 20 n g/injection) of ovariectomized rats. The trabecular bone volume was de creased in ovariectomized animals, but was not modified in TGF-beta(1) -injected bones in this short-term experiment. We conclude that, when injected into bones of ovariectomized rats, TGF-beta(1) attenuates the stimulation of osteoclastic resorption induced by estrogen deficiency . These data therefore suggest that a local failure of TGF-beta secret ion could be partly responsible for the stimulation of bone resorption and subsequent bone loss due to the cessation of the ovarian secretio n.