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.