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Low levels of cadmium exposure affect bone by inhibiting Lgr4 expression in osteoblasts and osteoclasts

Miaomiao Wang1, Jingjing Liu1, Guoying Zhu2

  • 1Department of Radiology, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing 210029, China.

Journal of Trace Elements in Medicine and Biology : Organ of the Society for Minerals and Trace Elements (GMS)
|June 30, 2022
PubMed
Abstract

Insights

Cadmium exposure harms bone by reducing Leucine-rich repeat containing GPCR-4 (LGR4) expression, which impairs bone formation and boosts osteoclast activity. This study clarifies cadmium

Area of Science:

  • Environmental toxicology
  • Bone biology
  • Cell signaling

Background:

  • Cadmium exposure is linked to bone loss, but mechanisms are unclear.
  • Leucine-rich repeat containing GPCR-4 (LGR4) regulates osteoclast formation and osteoblast activity.
  • Investigating LGR4's role in cadmium-induced bone loss is crucial.

Purpose of the Study:

  • To examine the effect of cadmium exposure on bone.
  • To investigate the role of LGR4 expression in cadmium-induced bone loss.
  • To elucidate the molecular mechanisms underlying cadmium's impact on bone metabolism.

Main Methods:

  • In vitro exposure of cells (RAW 264.7, primary osteoblasts) to cadmium.
  • Assessment of osteoclast formation and osteoblast activity.
  • Analysis of gene/protein expression (LGR4, RANKL, OPG, Traf6, NFATc1, AKT/ERK signaling) and in vivo rat model.

Main Results:

  • Cadmium inhibited osteoblast activity and promoted osteoclast formation.
  • Cadmium exposure decreased LGR4 expression in both cell types.
  • Cadmium upregulated AKT/ERK signaling; in vivo studies confirmed bone loss and reduced LGR4 expression.

Conclusions:

  • Cadmium induces bone loss by suppressing LGR4-mediated bone formation.
  • Cadmium promotes LGR4-related osteoclast formation, contributing to bone resorption.
  • LGR4 signaling is a key pathway affected by cadmium toxicity in bone.
Keywords:
CadmiumLeucine-rich repeat containing GPCR-4OsteoblastOsteoclastOsteoporosis

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