Fluoride Action Network



  • Short term exposure of mouse to sodium fluoride causes skeletal muscle hypertrophy.
  • Short term exposure causes upregulation of protein synthesis and PI3-AKT pathway.
  • Long term exposure of mouse to sodium fluoride causes muscle atrophy.
  • Long term exposure causes upregulation of Ubiquitin proteasome pathway.
  • Differential protein expression was seen in muscle exposed to sodium fluoride.


Fluoride at high doses is a well-known toxic agent for the musculoskeletal system, primarily in bone and cartilage cells. Research on fluoride toxicity concerning particularly on the skeletal muscle is scanty. We hypothesized that during skeletal fluorosis, along with bone, muscle is also affected, so we have evaluated the effects of Sodium fluoride (NaF) on mouse skeletal muscles. Sodium fluoride (80 ppm) was administered to 5-week-old C57BL6 mice drinking water for 15 and 60 days, respectively. We carried out histology, primary culture, molecular and proteomic analysis of fluoride administered mouse skeletal muscles. Results indicated an increase in the muscle mass (hypertrophy) in vivo and myotubes ex vivo by activating the IGF1/PI3/Akt/mTOR signalling pathway due to short term NaF exposure. The long-term exposure of mice to NaF caused loss of muscle proteins leading to muscle atrophy due to activation of the ubiquitin-proteasome pathway. Differentially expressed proteins were characterized and mapped using a proteomic approach. Moreover, the factors responsible for protein synthesis and PI3/Akt/mTOR pathway were upregulated, leading to muscle hypertrophy during the short term NaF exposure. Long term exposure to NaF resulted in down-regulation of metabolic pathways. Elevated myostatin resulted in the up-regulation of the muscle-specific E3 ligases-MuRF1, promoting the ubiquitination and proteasome-mediated degradation of critical sarcomeric proteins.

Graphical Abstract



Sodium fluoride
PI3/Akt/mTOR pathway
Skeletal muscle hypertrophy
Ubiquitin-proteasome pathway
Skeletal muscle atrophy

*Original abstract online at https://www.sciencedirect.com/science/article/abs/pii/S0304389422004435?via%3Dihub