Cytotoxic Properties of HT-2 Toxin in Human Chondrocytes: Could T<sub>3</sub> Inhibit Toxicity of HT-2?
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...
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| Format: | Article |
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MDPI AG
2019-11-01
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| Series: | Toxins |
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| Online Access: | https://www.mdpi.com/2072-6651/11/11/667 |
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| author | Feng’e Zhang Mikko Juhani Lammi Wanzhen Shao Pan Zhang Yanan Zhang Haiyan Wei Xiong Guo |
| author_facet | Feng’e Zhang Mikko Juhani Lammi Wanzhen Shao Pan Zhang Yanan Zhang Haiyan Wei Xiong Guo |
| author_sort | Feng’e Zhang |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-10T06:49:08Z |
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| institution | Directory Open Access Journal |
| issn | 2072-6651 |
| language | English |
| last_indexed | 2024-12-10T06:49:08Z |
| publishDate | 2019-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Toxins |
| spelling | doaj.art-ae236a3bae494b11831fbff6085ecb852022-12-22T01:58:35ZengMDPI AGToxins2072-66512019-11-01111166710.3390/toxins11110667toxins11110667Cytotoxic Properties of HT-2 Toxin in Human Chondrocytes: Could T<sub>3</sub> Inhibit Toxicity of HT-2?Feng’e Zhang0Mikko Juhani Lammi1Wanzhen Shao2Pan Zhang3Yanan Zhang4Haiyan Wei5Xiong Guo6School of Public Health, Health Science Center of Xi’an Jiaotong University, Key Laboratory of Trace Elements and Endemic Diseases, National Health Commission of the People’s Republic of China, Xi’an 710061, ChinaSchool of Public Health, Health Science Center of Xi’an Jiaotong University, Key Laboratory of Trace Elements and Endemic Diseases, National Health Commission of the People’s Republic of China, Xi’an 710061, ChinaSchool of Public Health, Health Science Center of Xi’an Jiaotong University, Key Laboratory of Trace Elements and Endemic Diseases, National Health Commission of the People’s Republic of China, Xi’an 710061, ChinaSchool of Public Health, Health Science Center of Xi’an Jiaotong University, Key Laboratory of Trace Elements and Endemic Diseases, National Health Commission of the People’s Republic of China, Xi’an 710061, ChinaSchool of Public Health, Health Science Center of Xi’an Jiaotong University, Key Laboratory of Trace Elements and Endemic Diseases, National Health Commission of the People’s Republic of China, Xi’an 710061, ChinaSchool of Public Health, Health Science Center of Xi’an Jiaotong University, Key Laboratory of Trace Elements and Endemic Diseases, National Health Commission of the People’s Republic of China, Xi’an 710061, ChinaSchool of Public Health, Health Science Center of Xi’an Jiaotong University, Key Laboratory of Trace Elements and Endemic Diseases, National Health Commission of the People’s Republic of China, Xi’an 710061, ChinaThyroid 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.https://www.mdpi.com/2072-6651/11/11/667triiodothyronineht-2 toxincytotoxicitykashin-beck disease |
| spellingShingle | Feng’e Zhang Mikko Juhani Lammi Wanzhen Shao Pan Zhang Yanan Zhang Haiyan Wei Xiong Guo Cytotoxic Properties of HT-2 Toxin in Human Chondrocytes: Could T<sub>3</sub> Inhibit Toxicity of HT-2? Toxins triiodothyronine ht-2 toxin cytotoxicity kashin-beck disease |
| title | Cytotoxic Properties of HT-2 Toxin in Human Chondrocytes: Could T<sub>3</sub> Inhibit Toxicity of HT-2? |
| title_full | Cytotoxic Properties of HT-2 Toxin in Human Chondrocytes: Could T<sub>3</sub> Inhibit Toxicity of HT-2? |
| title_fullStr | Cytotoxic Properties of HT-2 Toxin in Human Chondrocytes: Could T<sub>3</sub> Inhibit Toxicity of HT-2? |
| title_full_unstemmed | Cytotoxic Properties of HT-2 Toxin in Human Chondrocytes: Could T<sub>3</sub> Inhibit Toxicity of HT-2? |
| title_short | Cytotoxic Properties of HT-2 Toxin in Human Chondrocytes: Could T<sub>3</sub> Inhibit Toxicity of HT-2? |
| title_sort | cytotoxic properties of ht 2 toxin in human chondrocytes could t sub 3 sub inhibit toxicity of ht 2 |
| topic | triiodothyronine ht-2 toxin cytotoxicity kashin-beck disease |
| url | https://www.mdpi.com/2072-6651/11/11/667 |
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