Osteopontin--a molecule for all seasons.
Osteopontin (OPN) is a multifunctional protein, and although highly expressed in bone, it is also expressed by various cell types including macrophages, endothelial cells, smooth muscle cells and epithelial cells.1,,2 OPN is involved in diverse biological processes and the aim of this review is to give a broad outline of some important aspects of the biology of OPN. Although this review is written primarily from a renal perspective, it is hoped that the reader will appreciate that OPN is involved in both physiological and pathological processes in multiple organs and tissues including biomineralization, inflammation, leukocyte recruitment and cell survival.

OPN is a negatively‐charged acidic hydrophilic protein of approximately 300 amino acid residues, and is secreted into all body fluids. The OPN cDNA from various mammalian species exhibits a high degree of sequence homology. There is evidence of alternative splicing, although the functional significance of this is unclear at present. The molecule undergoes considerable post‐translational modification, and is phosphorylated and glycosylated. OPN has an arginine‐glycine‐aspartic acid (RGD) cell binding sequence, a calcium binding site and two heparin binding domains.

Cells may bind OPN via multiple integrin receptors including the vitronectin receptor ( α v β 3) as well as various β 1 and β 5 integrins. Integrin binding may be RGD‐dependent or ‐independent (e.g. via the motif SVVYGLR). OPN does not bind the standard form of CD44 (hyaluronic acid receptor) but does bind various isoforms of CD44. These CD44 isoforms bind OPN via multiple sites. OPN may be cleaved by thrombin, resulting in the exposure of additional cryptic binding sites as well as the production of functional chemotactic fragments.3

The regulation of OPN expression is incompletely understood at present and may differ between various cell types. Studies indicate that the OPN promoter contains various motifs including a purine‐rich …