FGF2 induced expression of the pyrophosphate generating enzyme, PC-1, is mediated by Runx2 and Msx2.

PC-1 is a nucleoside triphosphate pyrophosphohydrolase (NTPPPH) that generates pyrophosphate from the hydrolysis of ATP. PC-1 is the primary enzymatic generator of pyrophosphate in osteoblastic cells. The influence of PC-1 on tissue mineralization is complex (Figure 1). PC-1 activity increases extracellular levels of pyrophosphate. Pyrophosphate inhibits hydroxyapapatite crystal formation and propagation, yet PC-1 generated pyrophosphate also serves as an essential source of phosphate to enhance bone mineralization when it is hydrolyzed by the osteoblastic enzyme, alkaline phosphatase (AP). Additionally, while low pyrophosphate levels inhibit non-bone tissue calcification, dependent upon tissue composition, high pyrophosphate levels can lead to pathologic calcification of non-bone tissues. We previously showed that FGF2 specifically up-regulates PC-1 expression in MC3T3E1(C4) calvarial pre-osteoblasts, J Musculoskelet Neuronal Interact 2008; 8(4):318-320