Short‐term local injections of transforming growth factor‐β1 decrease ovariectomy‐stimulated osteoclastic resorption in vivo in rats

Abstract

Estrogen deficiency in rats is responsible for increased osteoclastic resorption and a subsequent rapid bone loss. TGF‐β, which is known to have acute effects on bone resorption in several in vitro models, has been shown to be secreted by osteoblastic cells in vitro in response to 17β‐estradiol, but little is known about its in vivo effects on bone resorption. We therefore decided to investigate the short‐term effect of TGF‐β1 on bone resorption in ovariectomized rats. TGF‐β1 (0.04–20 ng/injection), or vehicle, was injected daily directly 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 the secondary spongiosa of the metaphysis of injected femurs and compared with vehicle‐injected femurs of sham ovariectomized rats. Ovariectomy was associated with a marked increase in the resorption surface, a 2‐fold increase in the number of osteoclasts, and no change in the number of TRAP‐positive marrow cells distant from bone surfaces. Bone resorption was significantly lower in the TGF‐β1‐injected bones of ovariectomized rats, as compared with vehicle injected bones: the osteoclast 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‐β1 as compared with vehicle‐injected bones (mean ± SE, p < 0.05). The bone formation rate, assessed by double tetracycline labeling, was increased in ovariectomized rats, but was significantly decreased in TGF‐β1‐injected bones (2 and 20 ng/injection) of ovariectomized rats. The trabecular bone volume was decreased in ovariectomized animals, but was not modified in TGF‐β1‐injected bones in this short‐term experiment. We conclude that, when injected into bones of ovariectomized rats, TGF‐β1 attenuates the stimulation of osteoclastic resorption induced by estrogen deficiency. These data therefore suggest that a local failure of TGF‐β secretion could be partly responsible for the stimulation of bone resorption and subsequent bone loss due to the cessation of the ovarian secretion. Copyright © 1995 ASBMR