Phosphate: known and potential roles during development and regeneration of teeth and supporting structures

Inorganic phosphate (P(i)) is abundant in cells and tissues as an important component of nucleic acids and phospholipids, a source of high-energy bonds in nucleoside triphosphates, a substrate for kinases and phosphatases, and a regulator of intracellular signaling. The majority of the body's P(i) exists in the mineralized matrix of bones and teeth. Systemic P(i) metabolism is regulated by a cast of hormones, phosphatonins, and other factors via the bone-kidney-intestine axis. Mineralization in bones and teeth is in turn affected by homeostasis of P(i) and inorganic pyrophosphate (PPi), with further regulation of the P(i)/PP(i) ratio by cellular enzymes and transporters. Much has been learned by analyzing the molecular basis for changes in mineralized tissue development in mutant and knock-out mice with altered P(i) metabolism. This review focuses on factors regulating systemic and local P(i) homeostasis and their known and putative effects on the hard tissues of the oral cavity. By understanding the role of P(i) metabolism in the development and maintenance of the oral mineralized tissues, it will be possible to develop improved regenerative approaches.