It has been demonstrated that thyroid hormones stimulate osteoclasts indirectly and that this effect is mediated by products of other cell types present in bone. To determine if interleukin‐6 (IL‐6) could be a mediator of thyroid hormone action, we investigated the effect of 3,5,3′‐triiodothyronine (T3) on bone resorption (45Ca release) and on the IL‐6 concentration in medium from cultured 19‐day‐old fetal rat limb bones. T3 alone increased 45Ca release significantly only at a fairly high concentration (10−6 M) under the conditions used. T3 alone, over a 10−11–10−6 M concentration range, failed to elicit a detectable effect on the medium IL‐6 content. However, T3 potentiated the stimulatory effect of interleukin‐1β (IL‐1β) on IL‐6 production in a dose‐dependent manner. T3, 10−8 M, also significantly increased IL‐1β‐stimulated calcium release. Inhibition of IL‐1β with 1 μM interleukin‐1 receptor antagonist (IL‐Ira) abrogated the potentiating effects of T3 on IL‐1β‐stimulated IL‐6 production and blocked the combined effect of T3 and IL‐1β on 45Ca release. One micromolar indomethacin significantly, but not completely, inhibited the effect of IL‐1β, as well as the combined effect of IL‐1β and T3 on resorption and IL‐6 production, indicating the involvement of prostaglandins in these actions. Consistent with this, 1 μM prostaglandin E1 (PGE1) significantly increased both the IL‐6 production and the calcium release. By potentiating the effect of IL‐1β, T3 increased bone resorption at much lower concentrations. We therefore speculate that the enhancement of IL‐1β effects may be a biologically relevant mechanism of thyroid hormone action on bone.
ASJC Scopus subject areas
- Endocrinology, Diabetes and Metabolism
- Orthopedics and Sports Medicine