Fig. 1
From: A new perspective on intervertebral disc calcification—from bench to bedside
Schematic showing intradiscal calcification pathways. AF and EP present a heterotopic ectopic calcification nature – modulated by PPi metabolism - vs. NP, which shows a dystrophic nature, blinded to PPi metabolism changes. Bold proteins and lines – promote calcification. Dotted lines – inhibit calcification. Cross – no role in intradiscal calcification. Question mark – pathway still not explored in the disc. Proteins involved in extracellular PPi homeostasis. All PPi detected in the circulation originate from ENPP1-mediated conversion of extracellular ATP into AMP and PPi. The two main proteins involved in cellular ATP release for ENPP1-mediated PPi formation in plasma are ABCC6, primarily expressed in the liver, and ANK, ubiquitous. PPi is hydrolyzed to inorganic phosphate (Pi) in the periphery by the ecto-enzyme Tissue Non-specific Alkaline Phosphatase (TNAP). CD73 converts AMP into Pi and adenosine. The latter factor inhibits TNAP activity and, subsequently, PPi degradation. Although ENPP1 is only shown in the liver, this ecto-enzyme is ubiquitously expressed and released into blood plasma
