It will summarize findings from a large dataset which reported that chondrocalcinosis results from a systemic predisposition, and that the association between chondrocalcinosis and polymorphisms in ANKH gene is independent of age and osteoarthritis.
ANK is a multipass transmembrane protein transporter thought to play a role in the export of intracellular inorganic pyrophosphate and so to contribute to the pathophysiology of chondrocalcinosis.
ANK expression is also regulated by a variety of growth factors and cytokines that may further affect the transport of inorganic pyrophosphate and may be particularly relevant to the increased levels of expression of ANK in cartilage from chondrocalcinosis and osteoarthritis patients.
A subset of sporadic chondrocalcinosis appears to be heritable via a -4-bp G-to-A ANKH 5'-UTR transition that up-regulates expression of ANKH and extracellular PPi in chondrocyte cells.
This may be an overly simplistic view of this family of conditions, with recent evidence suggesting that, for example, ANKH variants may not all predispose to chondrocalcinosis by effects on PPi transport, but may also influence chondrocyte maturation.
ANKH, the human homolog of the mutated gene in the ank/ank mouse, has been implicated in familial autosomal-dominant chondrocalcinosis and autosomal-dominant craniometaphyseal dysplasia.
Increased ANK activity may explain the different types of crystals commonly deposited in human CCAL2 families and mutant mice and may provide a useful pharmacological target for treating some forms of human CC.