Low-Dose Tamoxifen Induces Significant Bone Formation in Mice
Zhihui Xie1, Cody McGrath1, Jeyantt Sankaran1
1Department of Medicine University of North Carolina Chapel Hill NC USA.
JBMR Plus
|March 29, 2021
Summary
Tamoxifen (TAM) treatment significantly increases bone formation in mice, even at low doses. This anabolic effect can confound studies using TAM for gene knockout, impacting bone phenotype interpretations.
Area of Science:
- Bone Biology
- Endocrinology
- Genetics
Background:
- Tamoxifen (TAM) is widely used to induce conditional gene expression in mouse models.
- Its effects on bone metabolism are not fully understood, particularly in the context of gene knockout studies.
Purpose of the Study:
- To investigate the dose-dependent effects of TAM on bone formation in mice.
- To determine if TAM itself is a confounding factor in studies of bone phenotypes.
Main Methods:
- Conditional knockout of β-catenin in Prrx1-CreER mice using TAM.
- Dose-response study of TAM (0-200 mg/kg) in wild-type mice.
- Analysis of bone volume using micro-computed tomography (μCT).
- Assessment of osteoblast and osteoclast markers.
Main Results:
- TAM significantly increased trabecular and cortical bone volume in a dose-dependent manner.
- Low TAM doses increased osteoclast surface, while high doses decreased it.
- Osteoblast marker expression increased with high TAM doses.
Conclusions:
- TAM administration has profound anabolic effects on bone formation.
- TAM treatment is a significant confounder in interpreting bone phenotypes in conditional knockout mouse models.
- Careful consideration of TAM dosage and its effects is crucial for experimental design.
