Polyphosphate regulates interleukin-11 levels of SaOS-2 cells

Abstract

Inorganic polyphoshate (polyP) is a linear polymer of orthophosphates (Pi) that varies in chain length from lessthan ten to several hundred residues. PolyP is a ubiquitous molecule in both prokaryotes and eukaryotes and has important physiological functions. Since its discovery in bacteria around 100 years ago, research has mainly been performed on prokaryotic functions with discoveries relating to polyphosphate function in survival and pathogen virulence. At present, the various functions of polyP in eukaryotes, especially in mammalian cells, are being elucidated. PolyP can play important roles in blood coagulation, inflammation, controlling mitochondrial calcium level thus affecting cell apoptosis and bone and cartilage formation. PolyP has been known to have relatively high concentrations in osteoblasts but the mechanisms for its action have been unknown. Here, we investigate the roles of polyP in signaling in cell culture studies of osteoblasts. We find polyP has significant influence on human‐osteoblast like SaoS‐2 cell proliferation and migration. Microarray studies showed a number of genes up and down‐regulated in response to polyP. In particular, we investigated interleukin‐11 in detail, and showed that interleukin‐11 is specifically upregulated at both RNA and protein levels in response to polyP, but not in response to orthophosphate, pyrophosphate or triphosphate, indicating specificity for long‐chain polyphosphate. Work is ongoing to unravel the crosstalk in signaling between inorganic polyphosphate and interleukin‐11.