Inorganic Polyphosphate and Its Chain-Length Dependency in Tissue Regeneration Including Bone Remodeling and Teeth Whitening

Abstract

Inorganic polyphosphate (polyP) is a phosphate polymer that exists in mammalian cells and tissues. Recently, important physiological functions of polyP were discovered, and some functions were dependent on its molecular size (chain length). We found that medium-length polyP that is composed of 60 phosphate residues on an average has cell proliferation-enhancing activity in vitro, whereas no such activity is observed for short-chain polyP with average chain length of around 14 residues. The medium-chain polyP enhances fibroblast growth factor (FGF) function, accelerates tissue regeneration and bone formation, and inhibits bone resorption by osteoclasts. Long-chain polyP also shows similar activity as medium-chain polyP but is a more efficient inhibitor of bone resorption and iNOS expression. In contrast, short-chain polyP is an efficient stain control agent that removes tooth stains and prevents stain deposition on tooth surface. Pyrophosphate and tripolyphosphate, which are much shorter than short-chain polyP, have decreased stain removal and prevention of stain deposition efficiency. The efficiency of long- and medium-chain polyP molecules also decreases depending on the chain length. The maximum stain-removing activity was reported for ultraphosphate that has a highly cross-linked mesh-like structure including a branched PO4 group in the molecule. These lines of evidence suggest that long- and medium-chain polyP are physiologically functional in mammals, and short-chain polyP and ultraphosphate are effective as stain-controlling agents for human teeth.