| Summary: | Thyroid hormone triiodothyronine (T<sub>3</sub>) plays an important role in coordinated endochondral ossification and hypertrophic differentiation of the growth plate, while aberrant thyroid hormone function appears to be related to skeletal malformations, osteoarthritis, and Kashin-Beck disease. The T-2 toxin, present extensively in cereal grains, and one of its main metabolites, HT-2 toxin, are hypothesized to be potential factors associated with hypertrophic chondrocyte-related osteochondropathy, known as the Kashin-Beck disease. In this study, we investigated the effects of T<sub>3</sub> and HT-2 toxin on human chondrocytes. The immortalized human chondrocyte cell line, C-28/I2, was cultured in four different groups: controls, and cultures with T<sub>3</sub>, T<sub>3</sub> plus HT-2 and HT-2 alone. Cytotoxicity was assessed using an MTT assay after 24-h-exposure. Quantitative RT-PCR was used to detect gene expression levels of <i>collagen types II</i> and <i>X</i>, <i>aggrecan</i> and <i>runx2</i>, and the differences in runx2 were confirmed with immunoblot analysis. T<sub>3</sub> was only slightly cytotoxic, in contrast to the significant, dose-dependent cytotoxicity of HT-2 alone at concentrations ≥ 50 nM. T<sub>3</sub>, together with HT-2, significantly rescued the cytotoxic effect of HT-2. HT-2 induced significant increases in <i>aggrecan</i> and <i>runx2</i> gene expression, while the hypertrophic differentiation marker, <i>type X collagen</i>, remained unchanged. Thus, T<sub>3</sub> protected against HT-2 induced cytotoxicity, and HT-2 was an inducer of the pre-hypertrophic state of the chondrocytes.
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