Recent studies have added to our knowledge regarding the mechanisms of calcium crystal deposition. Calcium pyrophosphate dihydrate (CPPD) crystal deposition is associated with elevated levels of PPi in joints. Cyclic compression of cartilage transiently elevated ATP levels in culture media. Extracellular ATP may be hydrolyzed by nucleoside triphosphate pyrophosphohydrolase (NTPPPH), yielding an elevated PPi concentration. CPPD crystal deposition increases with age. Nitric oxide may alter cartilage matrix by interfering with chondrocyte mitochondrial function and ATP production. Transglutaminase in adult, but not young, porcine articular chondrocytes was able to activate latent transforming growth factor beta, a potent stimulus to PPi production. Basic calcium phosphate crystals are more likely to form in a milieu of reduced PPi concentration. The ank gene mutation results in higher intracellular PPi concentration and lower extracellular concentration. The ANK protein is thought to be a transmembrane protein necessary for transport of PPi out of cells. A mutation that results in reduced synthesis of NTPPPH PC-1 caused infantile wrist and ankle periarticular calcification and vascular calcification.