TRIIODOTHYRONINE REGULATES THE PRODUCTION OF INTERLEUKIN-6 AND INTERLEUKIN-8 IN HUMAN BONE-MARROW STROMAL AND OSTEOBLAST-LIKE CELLS

Hyperthyroidism is associated with increased bone resorption but the m echanisms by which thyroid hormone (T3) affects bone cell metabolism r emain unclear. Recently it has been suggested that T3 stimulates osteo clastic resorption indirectly through the release of soluble mediators from osteoblasts. The aim of the present study was to investigate whe ther the TS-induced increase in bone resorption could be due to the re gulation of cytokine production by human osteoblasts (hOb). The effect s of T3 (1, 10, 100 nM) and IL-1 beta (100 U/ml) as the positive contr ol were examined on cytokine protein release and mRNA levels in cultur ed hOb cell lines (MG63, SaOs-2), primary hOb and human bone marrow st romal (hBMS) cells. T3 increased IL-6 and IL-8 mRNA levels as well as IL-6 and IL-8 protein release into the culture media from MG63 and hBM S cells in a time- and dose-dependent manner. The maximal effect on pr otein release in hBMS cells occurred at 24 h with a dose of T3 10 nM ( IL-6 5.5 +/- 1.1-fold above controls; IL-8 3.7 +/- 0.5-fold above cont rols, P<0.05). At the same time, mRNA levels in hBMS cells were increa sed 6.2 +/- 0.8-fold for IL-6 (P<0.05) and 5.7 +/- 0.8-fold for IL-8 ( P<0.05). Similar results were obtained in MG63 cells but no response w as seen in SaOs-2 or hOb cells despite measurable basal production. No r was there detectable regulation of IL-1 beta, IL-3, IL-11, IL-4 or g ranulocyte macrophage-colony stimulating factor by T3 in any cell type . In conclusion, T3 increases IL-6 and IL-8 production by MG63 and hBM S cells, suggesting that IL-6 and IL-8 may be T3-regulated genes in os teoblasts.