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

Abstract

Hyperthyroidism is associated with increased bone resorption but the mechanisms by which thyroid hormone (T3) affects bone cell metabolism remain unclear. Recently it has been suggested that T3 stimulates osteoclastic resorption indirectly through the release of soluble mediators from osteoblasts. The aim of the present study was to investigate whether the T3-induced increase in bone resorption could be due to the regulation of cytokine production by human osteoblasts (hOb).The effects of T3 (1, 10, 100 nM) and IL-1 (100 U/ml) as the positive control were examined on cytokine protein release and mRNA levels in cultured hOb cell lines (MG63, SaOs-2), primary hOb and human bone marrow stromal (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 hBMS cells in a time-and dose-dependent manner. The maximal effect on protein 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 controls, P<0·05). At the same time, mRNA levels in hBMS cells were increased 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 was seen in SaOs-2 or hOb cells despite measurable basal production. Nor was there detectable regulation of IL-1 , IL-3, IL-11, IL-4 or granulocyte macrophage-colony stimulating factor by T3 in any cell type.In conclusion, T3 increases IL-6 and IL-8 production by MG63 and hBMS cells, suggesting that IL-6 and IL-8 may be T3-regulated genes in osteoblasts.

Thyroid hormone stimulates basal and interleukin (IL)-1-induced IL-6 production in human bone marrow stromal cells: a possible mediator of thyroid hormone-induced bone loss

“…They also showed that bone turnover is increased and radius bone mineral content is reduced in patients with hyperthyroidism. Our results are also consistent with the report of Siddiqi et al (1998) demonstrating that T 3 increased both secretion and mRNA expression of IL-6 and IL-8 by hBMSCs and MG63 osteoblast-like cell lines. Tarjan & Stern (1994, 1995 reported that T 3 potentiated the stimulatory effect of IL-1 on IL-6 production in neonatal mouse calvarial osteoblasts and fetal rat limb bone cultures, which is in agreement with our results with hBMSCs.…”

Role and Mechanisms of Actions of Thyroid Hormone on the Skeletal Development

“…Earlier reports showed that T3 stimulated osteoclastic bone resorption in the presence of osteoblasts, but not in their absence (95)(96). These findings imply that TH indirectly stimulates osteoclasts via increased expression of RANKL and other cytokines involved in osteoclastogenesis including interleukin 6 (IL-6), IL-8 and prostaglandin E2 (PGE2) in osteoblasts (92,(97)(98). Several studies have demonstrated apparent expression of TR proteins in all bone cell lineages, however, it is not clear whether osteoclasts express TRα1 and TRβ1 mRNAs because currently available TR antibodies are of low affinity, thus compromising the detection of endogenous TRs (75,99).…”

Thyroid hormone stimulation of extracellular signal-regulated kinase and cell proliferation in human osteoblast-like cells is initiated at integrin αVβ3

“…In response to T 3 , osteoblasts are able to increase DNA synthesis and alkaline phosphatase activity (Sato et al 1987), osteocalcin production (Ohishi et al 1994) and cytokine synthesis (Siddiqi et al 1998). While the expression of TR isoforms has been documented in both rodent (Williams et al 1994) and human (Siddiqi et al 2002) osteoblast cell lines and primary cultures of rat (Bland et al 1997) and human (Siddiqi et al 2002) osteoblasts, there is only one report from more than a decade ago, which has provided evidence for non-genomic effects of T 3 on bone (Lakatos & Stern 1991).…”