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

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

  • Toxicon. 2022 Feb;207:13-20. doi: 10.1016/j.toxicon.2022.01.002.
Ying Zhang 1 Zhengzheng Li 2 Ying He 2 Meng Zhang 2 Yiping Feng 2 Qian Fang 2 Tianyou Ma 2 Xianghua Deng 3 Jinghong Chen 4
Affiliations

Affiliations

  • 1 School of Public Health, Health Science Center of Xi'an Jiaotong University, Key Laboratory of Trace Elements and Endemic Diseases of National Health and Family Planning Commission of the People's Republic of China, Collaborative Innovation Center of Endemic Diseases and Health Promotion in Silk Road Region, Xi'an, Shaanxi, 710061, PR China; School of Nursing, Health Science Center, Xi'an Jiaotong University, Xi'an, Shaanxi, PR China.
  • 2 School of Public Health, Health Science Center of Xi'an Jiaotong University, Key Laboratory of Trace Elements and Endemic Diseases of National Health and Family Planning Commission of the People's Republic of China, Collaborative Innovation Center of Endemic Diseases and Health Promotion in Silk Road Region, Xi'an, Shaanxi, 710061, PR China.
  • 3 Research Division, HSS, Research Institute, Hospital for Special Surgery, Weill Cornell Medical College, 535 East 70th Street, New York, NY, 10021, USA.
  • 4 School of Public Health, Health Science Center of Xi'an Jiaotong University, Key Laboratory of Trace Elements and Endemic Diseases of National Health and Family Planning Commission of the People's Republic of China, Collaborative Innovation Center of Endemic Diseases and Health Promotion in Silk Road Region, Xi'an, Shaanxi, 710061, PR China. Electronic address: [email protected].
Abstract

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.

Keywords

Collagens; Growth factor-β receptors; Hypertrophic chondrocytes; Kashin-beck disease; Matrix metalloproteinase; T-2 toxin.

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