Mini reviewOsteopontin: a versatile regulator of inflammation and biomineralization
Section snippets
Osteopontin structure, function and distribution
Osteopontin is a secreted glycoprotein with structural and functional characteristics of a matricellular protein (Fig. 1a). Osteopontin is aspartic acid-rich and may be highly phosphorylated on serines and threonines (depending on the tissue), endowing the protein with a highly acidic character. These features, combined with the presence of putative Ca2+ binding motifs, probably explain osteopontin's ability to bind rather large amounts of Ca2+ (∼50 Ca2+/mol.) and to interact with
Osteopontin and inflammation
A common theme in the normal and pathological expression of osteopontin is its dramatic upregulation within, and in proximity to, activated cells of the monocyte/macrophage lineage. These findings suggest an important role for osteopontin in these cell types, and indeed numerous correlative studies and in vitro findings have suggested that osteopontin may serve to modulate macrophage adhesion (Nasu et al., 1995, Giachelli et al., 1998), migration (Singh et al., 1990, Nasu et al., 1995,
Osteopontin and biomineralization
As mentioned earlier, osteopontin is highly expressed in mineralized tissues including bone and teeth. In fact, it is one of the most abundant non-collagenous proteins in bone. Furthermore, osteopontin is also invariably found in pathological calcifications of soft tissues (discussed in detail below). The association of osteopontin with biomineralization has led to a great number of studies aimed at elucidating its function in this process. At least three different functions of osteopontin in
Conclusions and future directions
In conclusion, a picture is emerging of osteopontin as an important regulator of monocyte/macrophage-derived cells in soft and hard tissue inflammation, mineralization, and remodeling. Functions of osteopontin in these cells may include, but are probably not limited to, regulation of cell adhesion, migration, differentiation, activation state, survival, and biomineralization. While we are just beginning to understand the importance of osteopontin in inflammatory and biomineralization processes,
Acknowledgements
Research in Dr Giachelli's lab is funded by grants from the NSF (EEC9529161) and National Institutes of Health (HL18645, DK47659, HL62329-01). Dr Giachelli is an American Heart Association Established Investigator. Susan Steitz was funded by a NIH Training grant (GM07037).
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