Elsevier

Matrix Biology

Volume 19, Issue 7, December 2000, Pages 615-622
Matrix Biology

Mini review
Osteopontin: a versatile regulator of inflammation and biomineralization

https://doi.org/10.1016/S0945-053X(00)00108-6Get rights and content

Abstract

Osteopontin is a secreted glycoprotein with a multidomain structure and functions characteristic of a matricellular protein. Osteopontin interacts with cell surface receptors via arginine–glycine–aspartate (RGD)- and non-RGD containing adhesive domains, in addition to binding to components of the structural extracellular matrix. While normally expressed in bone and kidney, osteopontin levels are elevated during wound healing and inflammation in most tissues studied to date. Since 1986, over one thousand studies have been published on osteopontin, including recent experiments in osteopontin-deficient mice. These studies reveal osteopontin as a cell adhesive, signaling, migratory, and survival stimulus for various mesenchymal, epithelial, and inflammatory cells, in addition to being a potent regulator of osseous and ectopic calcification. Based on these reports, a general picture of osteopontin as an important regulator of inflammation and biomineralization is emerging. A common denominator in osteopontin function in these situations is its ability to regulate the function of macrophage and macrophage-derived cells (i.e. osteoclasts). While we have learned much about osteopontin and the processes it appears to regulate over the past decade, many questions regarding this important multifunctional protein remain unanswered and provide important directions for future studies.

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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