Weighing the evidence for the roles of plasma versus local pyrophosphate in ectopic calcification disorders

Ralph, Douglas; Levine, Michael; Millán, José Luis; Uitto, Jouni; Li, Qiaoli

Affiliations

¹Genetics, Genomics and Cancer Biology Ph.D. Program, Jefferson College of Life Sciences, Thomas Jefferson University, Philadelphia, PA, USA

²Department of Dermatology and Cutaneous Biology, Sidney Kimmel Medical College, Jefferson Institute of Molecular Medicine, Thomas Jefferson University, Philadelphia, PA, USA

³PXE International Center of Excellence in Research and Clinical Care, Thomas Jefferson University, Philadelphia, PA, USA

⁴Division of Endocrinology, Children’s Hospital of Philadelphia, Philadelphia, PA, USA

⁵Sanford Children’s Health Research Center, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA, USA

Abstract and keywords

Ectopic calcification is characterized by inappropriate deposition of calcium mineral in nonskeletal connective tissues and can cause significant morbidity and mortality, particularly when it affects the cardiovascular system. Identification of the metabolic and genetic determinants of ectopic calcification could help distinguish individuals at the greatest risk of developing these pathological calcifications and could guide development of medical interventions. Inorganic pyrophosphate (PPᵢ) has long been recognized as the most potent endogenous inhibitor of biomineralization. It has been intensively studied as both a marker and a potential therapeutic for ectopic calcification. Decreased extracellular concentrations of PPᵢ have been proposed to be a unifying pathophysiological mechanism for disorders of ectopic calcification, both genetic and acquired. However, are reduced plasma concentrations of PPᵢ a reliable predictor of ectopic calcification? This perspective article evaluates the literature in favor and against a pathophysiological role of plasma versus tissue PPᵢ dysregulation as a determinant of, and as a biomarker for, ectopic calcification.

Keywords: ECTOPIC CALCIFICATION; INORGANIC PYROPHOSPHATE; ANIMAL MODELS; BIOMARKER

Links

DOI: 10.1002/jbmr.4791

PubMed: 36807615

WoS: 000948507100001

History

Received: 2022-12-16

Revised: 2023-02-02

Accepted: 2023-02-16

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