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Bone response to fluoride exposure is influenced by genetics.

Cláudia A N Kobayashi1, Aline L Leite1, Camila Peres-Buzalaf2

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Area of Science:

  • Biochemistry
  • Genetics
  • Orthopedics

Background:

  • Fluoride exposure impacts bone homeostasis and amelogenesis, but genetic influences on molecular mechanisms are unclear.
  • Dental fluorosis susceptibility and bone quality vary between mouse strains, suggesting a genetic component to fluoride response.

Purpose of the Study:

  • To investigate the molecular mechanisms underlying strain-specific bone responses to fluoride using a label-free proteomics approach.
  • To identify proteins involved in differential fluoride effects on bone formation and homeostasis in genetically distinct mouse strains.

Main Methods:

  • Utilized a label-free proteomics approach (LC-ESI-MS/MS) to analyze bone protein expression changes in 129P3/J and A/J mice exposed to varying fluoride (0, 10, 50 ppm) levels for 8 weeks.
  • Assessed in vivo bone formation via micro-CT analysis and measured mineral apposition rate (MAR) in cortical bone.
  • Evaluated plasma alkaline phosphatase activity and performed bone histomorphometry.

Main Results:

  • Fluoride exposure induced dose- and strain-specific alterations in bone protein expression, particularly in proteins related to osteogenesis and osteoclastogenesis.
  • While fluoride did not significantly affect bone mineral density or histomorphometry, the mineral apposition rate (MAR) was higher in resistant 129P3/J mice compared to susceptible A/J mice at 50 ppm fluoride.
  • Demonstrated that fluoride increased bone formation in a strain-specific manner, highlighting genetic control over bone response to fluoride.

Conclusions:

  • Confirms a significant genetic influence on bone response to fluoride exposure.
  • Identified specific bone proteins that may serve as targets for differential fluoride responses, offering insights into the molecular basis of fluoride sensitivity.