Tungsten accumulates in the intervertebral disc and vertebrae stimulating disc degeneration and upregulating markers of inflammation and pain

Eur Cell Mater. 2021 May 17:41:517-530. doi: 10.22203/eCM.v041a33.

Abstract

Tungsten is incorporated in many industrial goods, military applications and medical devices due to its ability to impart flexibility, strength and conductance to materials. Emerging evidence has questioned the safety of tungsten exposure as studies have demonstrated it can promote tumour formation, induce pulmonary disease and alter immune function. Although tungsten is excreted from the body it can accumulate in certain organs such as the brain, colon, liver, kidneys, spleen and bones, where most of the bioaccumulation occurs. Whether prolonged tungsten exposure leads to accumulation in other tissues is unknown. The present study demonstrated that mice exposed to 15 ppm sodium tungstate for 4 weeks in their drinking water showed comparable accumulation in both the bony vertebrae and intervertebral discs (IVDs). Lumbar IVD height was significantly reduced in tungsten-exposed mice and accompanied by decreased proteoglycan content and increased fibrosis. In addition to catabolic enzymes, tungsten also increased the expression of the inflammatory cytokines IL-1β and tumour necrosis factor (TNF)-α as well as the neurotrophic factors nerve growth factor (NGF) and brain-derived nerve factor (BDNF) in IVD cells. Tungsten significantly increased the presence of nociceptive neurons at the endplates of IVDs as observed by the expression of calcitonin gene-related peptide (CGRP) and anti-protein gene product 9.5 (PGP9.5) in endplate vessels. The present study provided evidence that tungsten may enhance disc degeneration and fibrosis as well as increase the expression of markers for pain. Therefore, tungsten toxicity may play a role in disc degeneration disease.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Biomarkers / metabolism
  • Cytokines / metabolism
  • Fibrosis / metabolism
  • Inflammation / metabolism*
  • Intervertebral Disc / drug effects*
  • Intervertebral Disc / metabolism
  • Intervertebral Disc Degeneration / chemically induced*
  • Intervertebral Disc Degeneration / metabolism
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Pain / metabolism*
  • Tungsten / adverse effects*
  • Up-Regulation / drug effects*

Substances

  • Biomarkers
  • Cytokines
  • Tungsten