Toxic effects of indoxyl sulfate on osteoclastogenesis and osteoblastogenesis

Jia Fwu Shyu, Wen Chih Liu, Cai Mei Zheng, Te Chao Fang, Yi Chou Hou, Chiz Tzung Chang, Ting Ying Liao, Yin Cheng Chen, Kuo Cheng Lu

Research output: Contribution to journalReview articlepeer-review

Abstract

Uremic toxins, such as indoxyl sulfate (IS) and kynurenine, accumulate in the blood in the event of kidney failure and contribute to further bone damage. To maintain the homeostasis of the skeletal system, bone remodeling is a persistent process of bone formation and bone resorption that depends on a dynamic balance of osteoblasts and osteoclasts. The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor that regulates the toxic effects of uremic toxins. IS is an endogenous AhR ligand and is metabolized from tryptophan. In osteoclastogenesis, IS affects the expression of the osteoclast precursor nuclear factor of activated T cells, cytoplasmic 1 (NFATc1) through AhR signaling. It is possible to increase osteoclast differentiation with short-term and low-dose IS exposure and to decrease differentiation with long-term and/or high-dose IS exposure. Co-incidentally, during osteoblastogenesis, through the AhR signaling pathway, IS inhibits the phos-phorylation of ERK, and p38 reduces the expression of the transcription factor 2 (Runx2), disturbing osteoblastogenesis. The AhR antagonist resveratrol has a protective effect on the IS/AhR pathway. Therefore, it is necessary to understand the multifaceted role of AhR in CKD, as knowledge of these transcription signals could provide a safe and effective method to prevent and treat CKD mineral bone disease.

Original languageEnglish
Article number11265
JournalInternational journal of molecular sciences
Volume22
Issue number20
DOIs
Publication statusPublished - Oct 1 2021

Keywords

  • Aryl hydrocarbon receptor
  • Bone remodeling
  • Indoxyl sulfate
  • Osteoblast
  • Osteoclast

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

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