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Related Concept Videos

Essential Minerals for Bone Health01:31

Essential Minerals for Bone Health

The minerals contained in all of the food we consume are essential for our organ systems. However, certain essential minerals, such as calcium, phosphorus, magnesium, manganese, and fluoride, largely affect bone health.
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Pharmacogenetics of Drug Targets: β₂-Adrenergic Receptors, Apo E, Thymidylate Synthase

Genetic polymorphisms in drug targets have emerged as critical determinants of interindividual variability in drug response and toxicity. Pharmacogenomic investigations increasingly focus on identifying these variations to personalize and optimize therapeutic interventions. A drug target may be a receptor, enzyme, or signaling protein involved in pharmacologic responses or disease-related pathways. While early pharmacogenetic studies focused primarily on drug metabolism, current research...
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Genetic variations significantly influence drug response through pharmacokinetics, receptor interactions, and biologic milieu modifications. Pharmacokinetic alterations impact drug metabolism and clearance, affecting efficacy and toxicity. Variants in drug-metabolizing enzymes, such as CYP2C9 and CYP2C19, alter drug activation and elimination. For example, CYP2C9 loss-of-function variants require lower warfarin doses to prevent excessive bleeding, while CYP2C19 variants reduce clopidogrel...
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Isolation, Purification, and Differentiation of Osteoclast Precursors from Rat Bone Marrow
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Published on: May 19, 2019

Genetic background influences fluoride's effects on osteoclastogenesis.

Dong Yan1, Aruna Gurumurthy, Maggie Wright

  • 1Dental Research, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA. dong_yan@dentistry.unc.edu

Bone
|October 16, 2007
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Summary

Fluoride (F) exposure impacts bone biology differently based on genetic background. This study reveals strain-specific effects on osteoclastogenesis and hematopoietic cell differentiation in mice, highlighting novel actions beyond fluoride's known anabolic effects.

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Published on: June 8, 2014

Area of Science:

  • Bone Biology and Physiology
  • Genetics and Genomics
  • Toxicology and Pharmacology

Background:

  • Fluoride (F) is known for its anabolic effects on bone, but its influence on osteoclastogenesis and genetic variability in bone cell response remains understudied.
  • Understanding genetic background's role in bone cell response to fluoride is crucial for assessing its therapeutic and toxicological potential.

Purpose of the Study:

  • To investigate the strain-specific effects of short-term fluoride (F) treatment on osteoclastogenesis and hematopoietic cell differentiation in C57BL/6J (B6) and C3H/HeJ (C3H) mice.
  • To compare the anabolic and resorptive actions of F across different genetic backgrounds.

Main Methods:

  • Four-week-old female B6 and C3H mice were administered NaF in drinking water (0, 50, 100 ppm F ion) for 3 weeks.
  • Bone marrow cells were analyzed for osteoclastogenesis and hematopoietic colony-forming assays.
  • Sera, femurs, tibiae, and lumbar vertebrae were assessed using biochemical markers, microCT, histology, and biomechanical testing.

Main Results:

  • B6 mice showed dose-dependent anabolic effects: increased serum ALP, bone mineral density (BMD), and decreased intact PTH and sRANKL.
  • C3H mice exhibited dose-dependent increases in osteoclast potential, osteoclast number, hematopoietic progenitor cells (CFU-GEMM, CFU-GM, CFU-M), and osteoclastogenic markers (PTH, RANKL, TRAP5b), with decreased OPG.
  • No significant effects on bone morphology, BMD, or mechanical properties were observed in C3H mice, suggesting limited bone resorption.

Conclusions:

  • Short-term fluoride treatment at physiological levels induces strain-specific effects in mice.
  • B6 mice displayed expected anabolic responses to fluoride.
  • C3H mice showed novel fluoride actions characterized by enhanced osteoclastogenesis and shifts in hematopoietic cell differentiation.