Increased FGFR3 is involved in T-2 toxin-induced lesions of hypertrophic cartilage associated with endemic osteoarthritis

Hum Exp Toxicol. 2023 Jan-Dec:42:9603271231219480. doi: 10.1177/09603271231219480.

Abstract

This study evaluated the effect of fibroblast growth factor receptor 3 (FGFR3) on damaged hypertrophic chondrocytes of Kashin-Beck disease (KBD). Immunohistochemical staining was used to evaluate FGFR3 expression in growth plates from KBD rat models and engineered cartilage. In vitro study, hypertrophic chondrocytes were pretreated by FGFR3 binding inhibitor (BGJ398) for 24 h before incubation at different T-2 toxin concentrations. Differentiation -related genes (Runx2, Sox9, and Col Ⅹ) and ECM degradation -related genes (MMP-13, Col Ⅱ) in the hypertrophic chondrocytes were analyzed using RT-PCR, and the corresponding proteins were analyzed using western blotting. Hypertrophic chondrocytes death was detected by the Annexin V/PI double staining assay. The integrated optical density of FGFR3 staining was increased in knee cartilage of rats and engineered cartilage treated with T-2 toxin. Both protein and mRNA levels of Runx2, Sox9, Col Ⅱ, and Col Ⅹ were decreased in a dose-dependent manner when exposed to the T-2 toxin and significantly upregulated by 1 μM BGJ398. The expression of MMP-1, MMP-9, and MMP-13 increased in a dose-dependent manner when exposed to T-2 toxin and significantly reduced by 1 μM BGJ398. 1 μM BGJ398 could prevent early apoptosis and necrosis induced by the T-2 toxin. Inhibiting the FGFR3 signal could alleviate extracellular matrix degradation, abnormal chondrocytes differentiation, and excessive cell death in T-2 toxin-induced hypertrophic chondrocytes.

Keywords: T-2 toxin; fibroblast growth factor receptor 3; kashin-beck disease.

MeSH terms

  • Animals
  • Cartilage, Articular*
  • Core Binding Factor Alpha 1 Subunit / metabolism
  • Core Binding Factor Alpha 1 Subunit / pharmacology
  • Kashin-Beck Disease* / chemically induced
  • Matrix Metalloproteinase 13 / genetics
  • Matrix Metalloproteinase 13 / metabolism
  • Osteoarthritis* / metabolism
  • Rats
  • Receptor, Fibroblast Growth Factor, Type 3 / genetics
  • Receptor, Fibroblast Growth Factor, Type 3 / metabolism
  • Receptor, Fibroblast Growth Factor, Type 3 / pharmacology
  • T-2 Toxin* / toxicity

Substances

  • infigratinib
  • T-2 Toxin
  • Matrix Metalloproteinase 13
  • Core Binding Factor Alpha 1 Subunit
  • Receptor, Fibroblast Growth Factor, Type 3