Endocrinology, Vol 134, 169-176, Copyright © 1994 by Endocrine Society

ARTICLES

Osteoblasts mediate thyroid hormone stimulation of osteoclastic bone resorption

JM Britto, AJ Fenton, WR Holloway and GC Nicholson
Department of Medicine, University of Melbourne, Geelong Hospital, Victoria, Australia.

Thyroid hormones increase bone turnover in vivo and stimulate bone resorption in vitro. Clinical states associated with excess circulating thyroid hormone levels are known to produce osteoporosis. To determine the effect of T3 on bone resorption, we used an isolated rat osteoclast bone resorption assay in the absence or presence of added osteoblasts. This makes it possible to distinguish between direct and indirect effects of thyroid hormones on osteoclasts. In short settlement osteoclast cultures, which contain relatively few osteoblasts, 24-h treatment with T3 (10(-10)-10(-8) M) produced no stimulation of bone resorption. However, after 48-h incubation in the presence of T3, an increase in resorption was observed (2.3-fold at 10(-9) M). In cocultures of osteoclasts and osteoblasts (UMR 106-01 osteoblast-like cells or long settlement cultures), T3 stimulated resorption at 24 h. Furthermore, stimulation of resorption occurred when osteoblasts (UMR 106-01 or rat calvarial cells) were pretreated with T3 and the subsequent osteoblast-osteoclast cocultures conducted for 24 h in the absence of T3. Thus, direct exposure of osteoclasts to T3 was not required for the stimulatory effect. Treatment for 48 h with T3 (10(-9) M) or PTH (10(-8) M) had no effect on bone resorption in osteoblast- free cultures derived from human osteoclastoma tumours. T4 was 100-fold less potent than T3 as a stimulator of osteoclast activity, and rT3 had no effect. T3-induced stimulation was inhibited by salmon calcitonin (10(-10) M). These findings indicate that thyroid hormone can act on osteoblasts to indirectly stimulate osteoclastic bone resorption.

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