How To Build a Bone: PHOSPHO1, Biomineralization, and Beyond

JBMR Plus
Scott DillonColin Farquharson

Abstract

Since its characterization two decades ago, the phosphatase PHOSPHO1 has been the subject of an increasing focus of research. This work has elucidated PHOSPHO1's central role in the biomineralization of bone and other hard tissues, but has also implicated the enzyme in other biological processes in health and disease. During mineralization PHOSPHO1 liberates inorganic phosphate (Pi) to be incorporated into the mineral phase through hydrolysis of its substrates phosphocholine (PCho) and phosphoethanolamine (PEA). Localization of PHOSPHO1 within matrix vesicles allows accumulation of Pi within a protected environment where mineral crystals may nucleate and subsequently invade the organic collagenous scaffold. Here, we examine the evidence for this process, first discussing the discovery and characterization of PHOSPHO1, before considering experimental evidence for its canonical role in matrix vesicle-mediated biomineralization. We also contemplate roles for PHOSPHO1 in disorders of dysregulated mineralization such as vascular calcification, along with emerging evidence of its activity in other systems including choline synthesis and homeostasis, and energy metabolism. © 2019 The Authors. JBMR Plus published by Wiley Periodicals, ...Continue Reading

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Citations

Apr 9, 2020·Calcified Tissue International·Munro Peacock
Jul 28, 2020·Calcified Tissue International·Sanjay Kumar Bhadada, Sudhaker D Rao
Nov 18, 2019·Clinica Chimica Acta; International Journal of Clinical Chemistry·Adrien NizetPer Magnusson
Feb 13, 2021·Cardiovascular Research·Magnus Bäck, Jean-Baptiste Michel
Feb 23, 2021·JBMR Plus·Scott DillonColin Farquharson
Apr 16, 2021·The Journal of Cell Biology·Elena A MayDavid U Mick
Jul 3, 2021·Calcified Tissue International·Katherine A StainesColin Farquharson

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Methods Mentioned

BETA
phosphotransferase
scanning electron microscopy

Software Mentioned

NRecon
Imaris

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