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. Epub 2022 Jan 5.

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.

MeSH terms

  • Cells, Cultured
  • Chondrocytes*
  • Humans
  • Hypertrophy
  • Receptors, Transforming Growth Factor beta
  • T-2 Toxin* / toxicity
  • Transforming Growth Factors

Substances

  • Receptors, Transforming Growth Factor beta
  • Transforming Growth Factors
  • T-2 Toxin