Phosphate (P)-regulated heterodimerization of the high-affinity sodium-dependent P transporters PiT1/Slc20a1 and PiT2/Slc20a2 underlies extracellular P sensing independently of P uptake.

Extracellular phosphate (P) can act as a signaling molecule that directly alters gene expression and cellular physiology. The ability of cells or organisms to detect changes in extracellular P levels implies the existence of a P-sensing mechanism that signals to the body or individual cell. However, unlike in prokaryotes, yeasts, and plants, the molecular players involved in P sensing in mammals remain unknown.

Mice with hypomorphic expression of the sodium-phosphate cotransporter PiT1/Slc20a1 have an unexpected normal bone mineralization.

The formation of hydroxyapatite crystals and their insertion into collagen fibrils of the matrix are essential steps for bone mineralization. As phosphate is a main structural component of apatite crystals, its uptake by skeletal cells is critical and must be controlled by specialized membrane proteins. In mammals, in vitro studies have suggested that the high-affinity sodium-phosphate cotransporter PiT1 could play this role.

Inorganic phosphate stimulates apoptosis in murine MO6-G3 odontoblast-like cells.

Objective: Dental pathologies such as caries are the most prevalent disease worldwide with infectious and social complications. During the process of caries formation, the tooth is degraded and demineralization of enamel and dentine leads to the release of large amounts of inorganic phosphate (Pi) within dental tubuli. As Pi has been shown to induce apoptosis in skeletal cells, including osteoblasts and chondrocytes, we questioned whether high concentrations of Pi could affect odontoblast viability, proliferation and apoptosis.

Phosphate-dependent stimulation of MGP and OPN expression in osteoblasts via the ERK1/2 pathway is modulated by calcium.

Inorganic phosphate (Pi) acts as a signaling molecule in bone-forming cells, affecting cell functions and gene expression. Particularly, Pi stimulates the expression of mineralization-associated genes such as matrix gla protein (MGP) and osteopontin (OPN) through the ERK1/2 pathway. With respect to the presence of elevated extracellular calcium and Pi levels during bone remodeling, we questioned whether calcium might play a role in the Pi-dependent effects in osteoblasts.

The emergence of phosphate as a specific signaling molecule in bone and other cell types in mammals.

Although considerable advances in our understanding of the mechanisms of phosphate homeostasis and skeleton mineralization have recently been made, little is known about the initial events involving the detection of changes in the phosphate serum concentrations and the subsequent downstream regulation cascade. Recent data has strengthened a long-established hypothesis that a phosphate-sensing mechanism may be present in various organs. Such a phosphate sensor would detect changes in serum or local phosphate concentration and would inform the body, the local environment, or the individual cell.