How to build a bone: PHOSPHO1, biomineralization and beyond

Dillon, Scott; Staines, Katherine A.; Mill�n, Jos� Luis; Farquharson, Colin

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.

Citation

Dillon, S., Staines, K. A., Millán, J. L., & Farquharson, C. (2019). How to build a bone: PHOSPHO1, biomineralization and beyond. Journal of Bone and Mineral Research Plus, 3(7), Article e10202. https://doi.org/10.1002/jbm4.10202

• Journal Article Type: Article
• Acceptance Date: May 6, 2019
• Online Publication Date: May 10, 2019
• Publication Date: 2019-07
• Deposit Date: May 9, 2019
• Publicly Available Date: May 10, 2019
• Journal: Journal of Bone and Mineral Research Plus
• Print ISSN: 2473-4039
• Publisher: Wiley
• Peer Reviewed: Peer Reviewed
• Volume: 3
• Issue: 7
• Article Number: e10202
• DOI: https://doi.org/10.1002/jbm4.10202
• Keywords: PHOSPHO1, phosphocholine, inorganic phosphate, biomineralization, matrix vesicle
• Public URL: http://researchrepository.napier.ac.uk/Output/1789359
• Contract Date: May 9, 2019