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

Abstract

Inorganic phosphate (Pi) 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 Pi exists in the mineralized matrix of bones and teeth. Systemic Pi 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 Pi and inorganic pyrophosphate (PPi), with further regulation of the Pi/PPi 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 Pi metabolism. This review focuses on factors regulating systemic and local Pi homeostasis and their known and putative effects on the hard tissues of the oral cavity. By understanding the role of Pi metabolism in the development and maintenance of the oral mineralized tissues, it will be possible to develop improved regenerative approaches.

Amelogenesis Imperfecta and Other Biomineralization Defects in Fam20a and Fam20c Null Mice

“…117 Hormones that specifically regulate P i homeostasis (''phosphatonins'') currently include fibroblast growth factor 23 (FGF23), and matrix extracellular phosphoglycoprotein (MEPE), as well molecules that affect FGF23 and MEPE function, such as phosphate-regulating gene with homologies to PHEX (phosphate-regulating gene with homologies to endopeptidases on the X chromosome) 14,15 and dentin matrix protein 1 (DMP1). 29 The principal phosphatonin is FGF23, which inhibits phosphate reabsorption by the sodium/phosphate cotransporter in the kidney, by acting through specific FGF receptors with the co-factor klotho protein. 72 FGF23 is made by osteocytes and activates KLOTHO/FGFR1 receptor heterodimers in the kidney to inhibit phosphate reabsorption and 1,25-dihydroxyvitamin D synthesis in the proximal renal tubules.…”

Calcium phosphate nanoparticles are associated with inorganic phosphate-induced osteogenic differentiation of rat bone marrow stromal cells

“…Inorganic phosphate (Pi) plays an essential role in diverse biological processes, including energy metabolism, cell signaling, nucleic acid synthesis, membrane function and bone mineralization [1]. As the second most abundant mineral ion found in the human body, Pi is not only a prerequisite for normal hydroxyapatite formation, it is also integral to osteoblast function during the differentiation process in vitro [2].…”

Correction of Hypophosphatasia‐Associated Mineralization Deficiencies In Vitro by Phosphate/Pyrophosphate Modulation in Periodontal Ligament Cells

“…1–3 Disorders arising from imbalance in the P i /PP i ratio have been reported to produce dissimilar effects on developing dental hard tissues, prompting the hypothesis that dental tissues are differentially sensitive to P i /PP i metabolism. 4, 5 In hypophosphatasia (HPP), deficiency of serum alkaline phosphatase activity (ALP) results from mutations in the liver/bone/kidney alkaline phosphatase gene (Alpl; OMIM 171760), encoding tissue nonspecific alkaline phosphatase (TNAP).…”