Effect of total flavonoids of Rhizoma Drynariae in thiram induced cytotoxicity of chondrocyte via BMP-2/Runx2 and IHH/PTHrP expressions

Ecotoxicol Environ Saf. 2020 Dec 15:206:111194. doi: 10.1016/j.ecoenv.2020.111194. Epub 2020 Aug 28.

Abstract

Tibial Dyschondroplasia (TD) is a prevailing skeletal disorder that mainly affects rapidly growing avian species. It results in reduced bone strength, lameness and an increase risk of fragility fractures. Total flavonoids of Rhizoma drynariae (TFRD) have been used as an effective treatment of different bone diseases in humans. The current in vitro study was conducted to explore the therapeutic effect of TFRD on thiram-induced cytotoxicity in avian growth plate cells via bone morphogenetic protein-2/runt related transcription factor-2 (BMP-2/Runx2) and Indian hedgehog/Parathyroid hormone-related peptide (IHH/PTHrP) expressions. Chondrocytes were isolated, cultured and refined from chicken's tibial growth plates in a special medium. Then chondrocytes were treated with sublethal thiram having less concentration (2.5 μg/mL) to induce cytotoxicity of chondrocyte, and then treated with providential doses (100 μg/mL) of TFRD. Thiram caused distorted morphology of chondrocytes, nuclei appeared disintegration or lysed along with decreased expressions of BMP-2/Runx2 and IHH/PTHrP. TFRD administration not only enhanced the viability of chondrocytes by itself, but also well restored the damage caused by thiram on growth plate chondrocytes by significantly up-regulating the expressions of BMP-2/Runx2 and IHH/PTHrP. Therefore, this study provides a novel insight into the further treatment of TD and other skeletal ailments and lays the foundation for prevention and treatment.

Keywords: BMP-2/Runx2; Chondrocyte; IHH/PTHrP; Rhizoma drynariae; Tibial dyschondroplasia.

MeSH terms

  • Animals
  • Bone Morphogenetic Protein 2 / genetics*
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Cells, Cultured
  • Chickens
  • Chondrocytes / drug effects*
  • Chondrocytes / metabolism
  • Chondrocytes / pathology
  • Core Binding Factor Alpha 1 Subunit / genetics
  • Flavonoids / isolation & purification
  • Flavonoids / pharmacology*
  • Gene Expression / drug effects*
  • Growth Plate / cytology
  • Growth Plate / drug effects
  • Hedgehog Proteins / genetics
  • Parathyroid Hormone-Related Protein / genetics
  • Polypodiaceae / chemistry*
  • Primary Cell Culture
  • Rhizome
  • Thiram / toxicity*
  • Up-Regulation

Substances

  • Bone Morphogenetic Protein 2
  • Core Binding Factor Alpha 1 Subunit
  • Flavonoids
  • Hedgehog Proteins
  • Parathyroid Hormone-Related Protein
  • Thiram