Transforming growth factor-β receptors mediates matrix degradation and abnormal hypertrophy in T-2 toxin-induced hypertrophic chondrocytes

• Published in: Toxicon (Oxford) 2022-02, Vol.207, p.13-20
• Main Authors: Zhang, Ying, Li, Zhengzheng, He, Ying, Zhang, Meng, Feng, Yiping, Fang, Qian, Ma, Tianyou, Deng, Xianghua, Chen, Jinghong
• Format: Article
• Language: English
• Subjects: Cells, Cultured; Chondrocytes; Collagens; Growth factor-β receptors; Humans; Hypertrophic chondrocytes; Hypertrophy; Kashin-beck disease; Matrix metalloproteinase; Receptors, Transforming Growth Factor beta; T-2 toxin; T-2 Toxin - toxicity; Transforming Growth Factors
• ISSN: 0041-0101; 1879-3150
• DOI: 10.1016/j.toxicon.2022.01.002

This study investigated whether transforming growth factor-β receptor I (TGF-βRI) and TGF-βRII mediate matrix degradation and abnormal hypertrophy in T-2 toxin-induced hypertrophic chondrocytes. Hypertrophic chondrocytes were exposed to TGF-βRI and TGF-βRII binding inhibitor (GW788388) for 24 h prior to exposure to different concentrations of T-2 toxin (0, 10, 25, and 50 ng/mL for 48 h). Hypertrophic chondrocytes were assessed based on the expression of matrix-degrading and terminal differentiation-related genes and cell viability. Matrix metalloproteinases (MMPs, MMP-13, MMP-1, and MMP-9) were reduced in the GW788388+T-2 toxin group compared to the T-2 toxin group. The expression of terminal differentiation-related genes (MMP-2, MMP-10, and collagen X) was increased in hypertrophic chondrocytes in the inhibited groups compared to that in the T-2 toxin group. The survival rate of chondrocytes decreased significantly in a dose-dependent manner. GW788388 did not significantly block the reduced cell viability in hypertrophic chondrocytes exposed to T-2 toxin. The upregulated expression of TGF-βRI and TGF-βRII mediates the abnormal chondrocyte hypertrophy and extracellular matrix degeneration observed in T-2 toxin-induced hypertrophic chondrocytes. [Display omitted] •T-2 toxin is considered to be the most toxic type A trichothecene mycotoxin.•T-2 toxin induces hypertrophic chondrocytes death, degradation of the matrix, and abnormal terminal differentiation.•TGF-βRs mediates matrix degradation and abnormal hypertrophy in T-2 toxin induced hypertrophic chondrocytes.