Osteoblasts mediate thyroid hormone stimulation of osteoclastic bone resorption.

Abstract

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.

Brain-immune interactions and disease susceptibility

“…223 Some studies also show the effects of thyroid hormones on bone remodeling in vitro, including bone resorption and formation. 224,225 More recently, Abe et al 226 have shown that TSH directly inhibits both osteoblastic bone formation and osteoclastic bone resorption.…”

Activation of the thyroid hormone receptor α gene promoter by the orphan nuclear receptor ERRα

“…Expression of both receptors have also been demonstrated for other tissues. For instance, TRa is present in osteoblasts (Sato et al, 1987) where it exerts pleiotropic roles in bone remodelling (Britto et al, 1994;Varga et al, 1994). Moreover, TRa7/7 mice appear to show impaired ossi®cation, resulting in a delayed bone development .…”

Tri-iodothyronine regulates the production of interleukin-6 and interleukin-8 in human bone marrow stromal and osteoblast-like cells

“…The mechanism for this effect of T3 on bone is not fully understood and in particular T3-responsive genes in bone cells have yet to be identified. Recent reports (Allain et al 1992, Britto et al 1994 have suggested that the effects of T3 on osteoclastic bone resorption are indirect and mediated by osteoblasts. T3 receptors (TR) have been demonstrated in rat, mouse and human osteoblast (hOb) cell lines (Sato et al 1987, Kasono et al 1988, Allain et al 1996 and it is thought that activation of these osteoblastic TRs results in the release of soluble agents which stimulate osteoclastic bone resorption (Klaushofer et al 1989, Lakatos & Stern 1992, Tarjan & Stern 1995.…”