IMR Press / FBL / Volume 10 / Issue 1 / DOI: 10.2741/1593

Frontiers in Bioscience-Landmark (FBL) is published by IMR Press from Volume 26 Issue 5 (2021). Previous articles were published by another publisher on a subscription basis, and they are hosted by IMR Press on imrpress.com as a courtesy and upon agreement with Frontiers in Bioscience.

Open Access Article

Inorganic pyrophosphate (PPI) in pathologic calcification of articular cartilage

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1 Rheumatology Section, San Diego Veterans Affairs Medical Center, University of California School of Medicine, VA Medical Center, 3350 La Jolla Village Drive, San Diego, CA 92161, USA

Academic Editor: Yubo Sun

Front. Biosci. (Landmark Ed) 2005, 10(1), 988–997; https://doi.org/10.2741/1593
Published: 1 January 2005
(This article belongs to the Special Issue Crystals-associated arthropathies and therapeutic development)
Abstract

Physiologic levels of extracellular PPi, which suppresses hydroxyapatite crystal growth, must be maintained by articular chondrocytes and resident cells in many othee tissues in order to prevent pathologic calcification. However, extracellular PPi rises in articular cartilage in direct association with aging. Matrix supersaturation with PPi stimulates chondrocalcinosis manifesting as calcium pyrophosphate dihydrate (CPPD) crystal deposition. Extracellular PPi levels are normally held in check by balances in PPi generation by nucleotide pyrophosphatase phosphodiesterase (NPP/NTPPPH) activity relative to PPi degradation by pyrophosphatases, by balance effects of cytokines and growth factors, and by transport of PPi from the cell interior involving the multiple-pass transmembrane protein ANK. But these mechanisms become dysrgulated in aging and osteoarthritic (OA) cartilage and extracellular PPi excess supervenes, mediated in large part by upregulated NPP1 and ANK expression in articular cartilage. Conversely, NPP1 and ANK deficiency states were recently linked to phenotypically similar forms of spontaneous soft tissue calcification with hydroxyapatite (HA). Here, we focus on recent advances in understanding of PPi metabolism and NPP1 and ANK function pertinent to the pathogenesis of pathologi matrix calcification in articular cartilage.

Keywords
Inorganic Pyrophosphate
Pathology
Calcification
Articular Cartilage
Chondrocyte
Review
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