Modulation of chondrocyte production of extracellular inorganic pyrophosphate.
OBJECTIVE
Extracellular inorganic pyrophosphate (ePPi) both inhibits and promotes different forms of pathologic mineralization. Basic calcium phosphate (BCP) deposition results from depressed levels of ePPi while excess levels of ePPi leads to calcium pyrophosphate dihydrate crystal deposition (CPPD) disease. These crystals are also often identified in patients with osteoarthritis, the most prevalent form of arthritis causing significant morbidity.


METHODS
The two primary hypotheses for generation of ePPi, export of inorganic pyrophosphate through the multipass transmembrane protein ANK and generation of ePPi by ectoenzyme activity, continue to be supported and better understood through animal models and study of families with CPPD deposition disease.


CONCLUSIONS
As the pathophysiology of crystal formation in both articular cartilage and synovial fluid is better understood, the opportunity for prevention and treatment of pathologic mineralization increases. In particular, a more complex understanding of the ank gene, ectoenzyme PC-1, and the transglutaminase enzyme family may eventually translate into therapeutic application for both BCP deposition and CPPD deposition disease.
Costello
Jill C
JC
Division of Rheumatology, Medical College of Wisconsin, 9200 West Wisconsin Avenue, Milwaukee, WI 53226, USA. jcostell@mail.mcw.edu
Ryan
Lawrence M
LM
D002130:Calcium Phosphates / Q000378:metabolism; D002131:Calcium Pyrophosphate / Q000378:metabolism*; D002358:Cartilage, Articular / Q000378:metabolism / Q000503:physiopathology; D002805:Chondrocalcinosis / Q000378:metabolism*; D019902:Chondrocytes / Q000378:metabolism*; D003460:Crystallization; D011756:Diphosphates / Q000378:metabolism*; D005110:Extracellular Space / Q000378:metabolism; D006801:Humans; D010727:Phosphoric Diester Hydrolases / Q000378:metabolism; D011755:Pyrophosphatases / Q000378:metabolism; D013582:Synovial Fluid / Q000378:metabolism; D011503:Transglutaminases / Q000378:metabolism
D002130:Calcium Phosphates; D011756:Diphosphates; C020243:calcium phosphate; D011503:Transglutaminases; D010727:Phosphoric Diester Hydrolases; C065962:ectonucleotide pyrophosphatase phosphodiesterase 1; D011755:Pyrophosphatases; D002131:Calcium Pyrophosphate