Overexpression of Secreted Frizzled-Related Protein 1 Inhibits Bone Formation and Attenuates Parathyroid Hormone Bone Anabolic Effects
2010

Impact of sFRP1 Overexpression on Bone Formation and PTH Effects

Sample size: 22 publication Evidence: high

Author Information

Author(s): Yao Wei, Cheng Zhiqiang, Shahnazari Mohammad, Dai Wewei, Johnson Mark L, Lane Nancy E

Primary Institution: UC Davis Medical Center

Hypothesis

Overexpression of sFRP1 in sFRP1 transgenic mice would reduce osteoblast number and activity, leading to lower peak bone mass and reduced bone acquisition.

Conclusion

Overexpression of sFRP1 inhibits bone formation and attenuates the anabolic effects of parathyroid hormone on bone.

Supporting Evidence

  • Trabecular bone mass was significantly lower in sFRP1 Tg mice compared to wild-type controls.
  • Bone formation markers decreased significantly in sFRP1 Tg mice.
  • PTH treatment increased bone volume in wild-type mice but had minimal effects in sFRP1 Tg mice.
  • Surface-based bone formation decreased by 68% in female and 48% in male sFRP1 Tg mice compared to controls.
  • Active β-catenin levels were significantly lower in sFRP1 Tg mice.

Takeaway

Mice with too much sFRP1 have weaker bones and don't grow as strong when given a hormone that usually helps bones grow.

Methodology

The study involved evaluating skeletal phenotype, measuring bone mass and microarchitecture using micro-computed tomography, and assessing osteoblastic and osteoclastic cell maturation in primary bone marrow cell cultures.

Limitations

The study only evaluated 12- to 14-week-old animals and did not assess age-related changes or the effects of longer PTH treatment.

Participant Demographics

The study involved both male and female mice.

Statistical Information

P-Value

p<0.05

Statistical Significance

p<0.05

Digital Object Identifier (DOI)

10.1359/jbmr.090719

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