Mechanisms of Thyroid Hormone-Induced Osteoporosis

摘要

Thyroid hormone (T3) is essential for skeletal growth and development. Excess T3, especially in adults, can cause bone loss and increased fracture susceptibility. Our previous data showed that T3 increases local production of a critical bone growth factor, insulin-like growth factor-I (IGF- I), and potentiates interleukin-1 (IL-I)-stimulated production of the osteoclastogenic cytokine interleukin-6 (IL-6). The current proposal was to determine whether these local factors are important in the effects of T3 to stimulate osteoblast proliferation and to generate bone-phenotypic proteins, i. e. alkaline phosphatase, osteocalcin, collagen, and in the resorptive effects of T3. The data obtained support these conclusions: antibody, antagonist peptide or antisense oligonucleotide to the IGF-I receptor prevented the anabolic effects of T3, and antibody to the IL-6 receptor inhibited the bone-resorbing effect of T3. A second goal was to investigate the mechanisms by which T3 stimulates production of IGF-I and IL-6. T3 had small stimulatory effects and enhanced the effect of IL-i to increase IL-6 mRNA and IL-6 promoter construct expression. T3 had small stimulatory effects on IGF-I mRNA expression. Thus, transcriptional effects contribute to the actions of T3 to increase both local factors. T3 interacted with PTH, increasing PTH receptor expression and augmenting PTH signaling in osteoblastic cells.