Abstract
ABSTRACTSince 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, Inc. on behalf of American Society for Bone and Mineral Research.
Highlights
Biomineralization of the skeleton is a fundamental process indispensable for health and wellbeing throughout life
The vertebrate skeleton is a complex organ that performs varied and diverse functions encompassing its action as a biomechanical and protective scaffold in conjunction with the musculature, its role in calcium and phosphate ion homeostasis, and recent evidence demonstrating its capacity as an endocrine organ involved with energy homeostasis.[1]. At the level of molecular constituents bone is composed of a combination of inorganic mineral, type I collagen, noncollagenous proteins (NCPs), and water, arranged into an extremely ordered hierarchical structure.[2]. The fine details of this architecture remain controversial at the nanostructural level,(3) with respect to differences between embryonic and mature tissue; the mineral phase has come to be regarded as a poorly‐crystalline substituted hydroxyapatite phase, mainly composed of calcium phosphate
tissue nonspecific alkaline phosphatase (TNAP) activity has long been implicated in the mineralization process, it is recognized that TNAP is only one component and the full story requires a more complex biochemical system
Summary
Biomineralization of the skeleton is a fundamental process indispensable for health and wellbeing throughout life.
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
