Cytotoxic Properties of HT-2 Toxin in Human Chondrocytes: Could T3 Inhibit Toxicity of HT-2?

Feng’E Zhang,Xiong Guo,Wanzhen Shao,Pan Zhang,Mikko Juhani Lammi,Haiyan Wei,Yanan Zhang

doi:10.3390/toxins11110667

Abstract

Thyroid hormone triiodothyronine (T3) 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 T3 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 T3, T3 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 collagen types II and X, aggrecan and runx2, and the differences in runx2 were confirmed with immunoblot analysis. T3 was only slightly cytotoxic, in contrast to the significant, dose-dependent cytotoxicity of HT-2 alone at concentrations ≥ 50 nM. T3, together with HT-2, significantly rescued the cytotoxic effect of HT-2. HT-2 induced significant increases in aggrecan and runx2 gene expression, while the hypertrophic differentiation marker, type X collagen, remained unchanged. Thus, T3 protected against HT-2 induced cytotoxicity, and HT-2 was an inducer of the pre-hypertrophic state of the chondrocytes.

Highlights

IntroductionBy deiodinase 2 (DIO2), and it is known to be an essential regulator in metabolism, growth, and development of the human body, and it is critical for the maturation of the skeletal system [1]
Thyroid hormone is converted to this active form from thyroxine (T4 )by deiodinase 2 (DIO2), and it is known to be an essential regulator in metabolism, growth, and development of the human body, and it is critical for the maturation of the skeletal system [1].It controls the linear growth of bone by regulating endochondral ossification and promotes chondrocyte maturation and hypertrophic differentiation [2]
MTT assay was used to evaluate the cytotoxicity in C-28/I2 chondrocyte cultures treated with T3 at concentrations ranging from 0 to 1000 nM

Summary

Introduction

By deiodinase 2 (DIO2), and it is known to be an essential regulator in metabolism, growth, and development of the human body, and it is critical for the maturation of the skeletal system [1]. It controls the linear growth of bone by regulating endochondral ossification and promotes chondrocyte maturation and hypertrophic differentiation [2]. A body of evidence implies that T3 has significant effects on cartilage and chondrocyte physiology. It is worth mentioning that up-regulated DIO2 expression has been observed in osteoarthritic human articular cartilage and transgenic mice overexpressing

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