Loss of Skeletal Mineralization by the Simultaneous Ablation of PHOSPHO1 and Alkaline Phosphatase Function: A Unified Model of the Mechanisms of Initiation of Skeletal Calcification
2011

Role of PHOSPHO1 in Bone Mineralization

publication Evidence: high

Author Information

Author(s): Yadav Manisha C, Simão Ana Maria Sper, Narisawa Sonoko, Huesa Carmen, McKee Marc D, Farquharson Colin, Millán José Luis

Primary Institution: Sanford Children's Health Research Center, Sanford-Burnham Medical Research Institute

Hypothesis

PHOSPHO1 plays a crucial role in the initiation of skeletal calcification.

Conclusion

The study concludes that PHOSPHO1 has a nonredundant functional role during endochondral ossification, and its ablation leads to severe skeletal mineralization defects.

Supporting Evidence

  • PHOSPHO1 is expressed at much higher levels in mineralizing tissues compared to nonmineralizing tissues.
  • Phospho1−/− mice exhibit significant skeletal abnormalities including scoliosis and spontaneous fractures.
  • Transgenic overexpression of alkaline phosphatase does not correct the bone phenotype in Phospho1−/− mice.
  • Double ablation of PHOSPHO1 and alkaline phosphatase leads to complete absence of skeletal mineralization.

Takeaway

This study shows that a protein called PHOSPHO1 is very important for bones to grow properly. Without it, bones can't harden and grow like they should.

Methodology

The study used genetically modified mice to analyze the effects of PHOSPHO1 and alkaline phosphatase deficiencies on bone mineralization.

Limitations

The study primarily focuses on mouse models, which may not fully replicate human conditions.

Statistical Information

P-Value

p<0.05

Statistical Significance

p<0.05

Digital Object Identifier (DOI)

10.1002/jbmr.195

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