A Fragile Phosphate/Pyrophosphate Balance: From Essential Mineralization to Rare Calcifying Diseases

Reznikov N, Hoac B, Buss DJ, Addison WN, Barros NMT, McKee MD. Biological stenciling of mineralization in the skeleton: local enzymatic removal of inhibitors in the extracellular matrix. Bone. 2020;138:115447.

CAS  PubMed  Google Scholar 

McKee MD, Buss DJ, Reznikov N. Mineral tessellation in bone and the stenciling principle for extracellular matrix mineralization. J Struct Biol. 2022;214:107823.

CAS  PubMed  Google Scholar 

Zhang J, Ma Z, Yan K, Wang Y, Yang Y, Wu X. Matrix Gla protein promotes the bone formation by up-regulating Wnt/β-Catenin signaling pathway. Front Endocrinol. 2019;10:891.

Google Scholar 

Zhang Y, Zhao L, Wang N, Li J, He F, Li X, et al. Unexpected role of matrix Gla protein in osteoclasts: inhibiting osteoclast differentiation and bone resorption. Mol Cell Biol. 2019;39:e00012–19.

CAS  PubMed  PubMed Central  Google Scholar 

Si J, Wang C, Zhang D, Wang B, Zhou Y. Osteopontin in bone metabolism and bone diseases. Med Sci Monit. 2020;26:e919159.

CAS  Google Scholar 

Shimada T, Hasegawa H, Yamazaki Y, Muto T, Hino R, Takeuchi Y, et al. FGF-23 is a potent regulator of vitamin D metabolism and phosphate homeostasis**. J Bone Min Res. 2004;19:429–35.

CAS  Google Scholar 

Lafage-Proust M-H, Magne D. Biology of bone mineralization and ectopic calcifications: the same actors for different plays. Arch Pédiatrie. 2024;31:S43–12.

Google Scholar 

Rashdan NA, Rutsch F, Kempf H, Váradi A, Lefthériotis G, MacRae VE. New perspectives on rare connective tissue calcifying diseases. Curr Opin Pharmacol. 2016;28:14–23.

CAS  PubMed  Google Scholar 

Fleisch H, Bisaz S. Isolation from urine of pyrophosphate, a calcification inhibitor. Am J Physiol. 1962;203:671–5.

CAS  Google Scholar 

Kelly SJ, Dardinger DE, Butler LG. Hydrolysis of phosphonate esters catalyzed by 5’-nucleotide phosphodiesterase. Biochemistry. 1975;14:4983–8.

CAS  PubMed  Google Scholar 

Terkeltaub R, Rosenbach M, Fong F, Goding J. Causal link between nucleotide pyrophosphohydrolase overactivity and increased intracellular inorganic pyrophosphate generation demonstrated by transfection of cultured fibroblasts and osteoblasts with plasma cell membrane glycoprotein-1. Relevance to calcium pyrophosphate dihydrate deposition disease. Arthritis Rheum. 1994;37:934–41.

CAS  PubMed  Google Scholar 

Ferreira CR, Carpenter TO, Braddock DT. ENPP1 in blood and bone: skeletal and soft tissue diseases induced by ENPP1 deficiency. Annu Rev Pathol. 2024;19:507–40.

CAS  PubMed  Google Scholar 

Jansen RS, Küçükosmanoğlu A, de Haas M, Sapthu S, Otero JA, Hegman IEM, et al. ABCC6 prevents ectopic mineralization seen in pseudoxanthoma elasticum by inducing cellular nucleotide release. Proc Natl Acad Sci U S A. 2013;110:20206–11.

CAS  PubMed  PubMed Central  Google Scholar 

Favre G, Laurain A, Aranyi T, Szeri F, Fulop K, Le Saux O, et al. The ABCC6 transporter: a new player in biomineralization. Int J Mol Sci. 2017;18:1941.

PubMed  PubMed Central  Google Scholar 

Szeri F, Lundkvist S, Donnelly S, Engelke UFH, Rhee K, Williams CJ, et al. The membrane protein ANKH is crucial for bone mechanical performance by mediating cellular export of citrate and ATP. PLOS Genet. 2020;16:e1008884.

CAS  PubMed  PubMed Central  Google Scholar 

Szeri F, Niaziorimi F, Donnelly S, Fariha N, Tertyshnaia M, Patel D, et al. The mineralization regulator ANKH mediates cellular efflux of ATP, not pyrophosphate. J Bone Min Res. 2022;37:1024–31.

CAS  Google Scholar 

Fleisch H, Bisaz S. Mechanism of calcification: inhibitory role of pyrophosphate. Nature. 1962;195:911–911.

CAS  PubMed  Google Scholar 

Sekaran S, Vimalraj S, Thangavelu L. The physiological and pathological role of tissue nonspecific alkaline phosphatase beyond mineralization. Biomolecules. 2021;11:1564.

CAS  PubMed  PubMed Central  Google Scholar 

St Hilaire C, Ziegler SG, Markello TC, Brusco A, Groden C, Gill F, et al. NT5E mutations and arterial calcifications. N Engl J Med. 2011;364:432–42.

CAS  PubMed  PubMed Central  Google Scholar 

Jin H, St Hilaire C, Huang Y, Yang D, Dmitrieva NI, Negro A, et al. Increased activity of TNAP compensates for reduced adenosine production and promotes ectopic calcification in the genetic disease ACDC. Sci Signal. 2016;9:ra121.

PubMed  PubMed Central  Google Scholar 

Millán JL. The role of phosphatases in the initiation of skeletal mineralization. Calcif Tissue Int. 2013;93:299–306.

PubMed  Google Scholar 

Beck L, Beck-Cormier S. Extracellular phosphate sensing in mammals: what do we know? J Mol Endocrinol. 2020;65:R53–63.

CAS  PubMed  Google Scholar 

Villa-Bellosta R, Ravera S, Sorribas V, Stange G, Levi M, Murer H, et al. The Na+-Pi cotransporter PiT-2 (SLC20A2) is expressed in the apical membrane of rat renal proximal tubules and regulated by dietary Pi. Am J Physiol Ren Physiol. 2009;296:F691–699.

CAS  Google Scholar 

Suzuki A, Ghayor C, Guicheux J, Magne D, Quillard S, Kakita A, et al. Enhanced expression of the inorganic phosphate transporter Pit-1 is involved in BMP‐2–induced matrix mineralization in osteoblast‐like cells. J Bone Min Res. 2006;21:674–83.

CAS  Google Scholar 

Legati A, Giovannini D, Nicolas G, López-Sánchez U, Quintáns B, Oliveira JRM, et al. Mutations in XPR1 cause primary familial brain calcification associated with altered phosphate export. Nat Genet. 2015;47:579–81.

CAS  PubMed  PubMed Central  Google Scholar 

Germain DP. Pseudoxanthoma elasticum. Orphanet J Rare Dis. 2017;12:85.

PubMed  PubMed Central  Google Scholar 

Li Q, van de Wetering K, Uitto J. Pseudoxanthoma elasticum as a paradigm of heritable ectopic mineralization disorders: pathomechanisms and treatment development. Am J Pathol. 2019;189:216–25.

PubMed  PubMed Central  Google Scholar 

Pfau K, Lengyel I, Ossewaarde-van Norel J, van Leeuwen R, Risseeuw S, Leftheriotis G, et al. Pseudoxanthoma elasticum - genetics, pathophysiology, and clinical presentation. Prog Retin Eye Res. 2024;102:101274.

CAS  PubMed  PubMed Central  Google Scholar 

Le Saux O, Urban Z, Tschuch C, Csiszar K, Bacchelli B, Quaglino D, et al. Mutations in a gene encoding an abc transporter cause pseudoxanthoma elasticum. Nat Genet. 2000;25:223–7.

PubMed  Google Scholar 

Bergen AA, Plomp AS, Schuurman EJ, Terry S, Breuning M, Dauwerse H, et al. Mutations in ABCC6 cause pseudoxanthoma elasticum. Nat Genet. 2000;25:228–31.

CAS  PubMed  Google Scholar 

Ringpfeil F, Lebwohl MG, Christiano AM, Uitto J. Pseudoxanthoma elasticum: mutations in the MRP6 gene encoding a transmembrane ATP-binding cassette (ABC) transporter. Proc Natl Acad Sci U S A. 2000;97:6001–6.

CAS  PubMed  PubMed Central  Google Scholar 

Luo H, Faghankhani M, Cao Y, Uitto J, Li Q. Molecular genetics and modifier genes in pseudoxanthoma elasticum, a heritable multisystem ectopic mineralization disorder. J Invest Dermatol. 2021;141:1148–56.

CAS  PubMed  Google Scholar 

Bartstra JW, Risseeuw S, de Jong PA, van Os B, Kalsbeek L, Mol C, et al. Genotype-phenotype correlation in pseudoxanthoma elasticum. Atherosclerosis. 2021;324:18–26.

CAS  PubMed  Google Scholar 

Jansen RS, Duijst S, Mahakena S, Sommer D, Szeri F, Váradi A, et al. ABCC6–mediated ATP secretion by the liver is the main source of the mineralization inhibitor inorganic pyrophosphate in the systemic circulation—brief report. Arterioscler Thromb Vasc Biol. 2014;34:1985–9.

CAS  PubMed  PubMed Central  Google Scholar 

Nitschke Y, Baujat G, Botschen U, Wittkampf T, du Moulin M, Stella J, et al. Generalized arterial calcification of infancy and pseudoxanthoma elasticum can be caused by mutations in either ENPP1 or ABCC6. Am J Hum Genet. 2012;90:25–39.

CAS  PubMed  PubMed Central  Google Scholar 

Ralph D, Nitschke Y, Levine MA, Caffet M, Wurst T, Saeidian AH, et al. ENPP1 variants in patients with GACI and PXE expand the clinical and genetic heterogeneity of heritable disorders of ectopic calcification. PLoS Genet. 2022;18:e1010192.

CAS  PubMed  PubMed Central  Google Scholar 

Gorgels TGMF, Hu X, Scheffer GL, van der Wal AC, Toonstra J, de Jong PTVM, et al. Disruption of Abcc6 in the mouse: novel insight in the pathogenesis of pseudoxanthoma elasticum. Hum Mol Genet. 2005;14:1763–73.

CAS  PubMed  Google Scholar 

Li Q, Kingman J, Wetering K, van de, Tannouri S, Sundberg JP, Uitto J. Abcc6 knockout rat model highlights the role of liver in PPi homeostasis in pseudoxanthoma elasticum. J Invest Dermatol. 2017;137:1025–32.

CAS 

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