Biomaterials Tutorial

Osteopontin

Rupak Rajachar
University of Washington Department of Bioengineering

Osteopontin (OPN) is a secreted phosphorylated glycoprotein.  It is most prominently expressed in bone by osteoblasts (bone-forming cells) and osteoclasts (bone-resorbing cells). It is also expressed by many other cell types including macrophages, endothelial cells, and smooth musclecells. Important structural elements of OPN include an arginine-glycine-aspartic acid (RGD) cell-binding domain (yellow), putative calcium-binding motifs (green), and numerous serine and threonine phosphorylation sites (P) (FIGURE 1) [1].

Figure 1.

OPN mediatesnormal biological (physiologic) and disease related (pathologic) processes including biomineralization, inflammation, macrophagerecruitment and cell survival. Biomineralization is the deposition of calcium phosphate based mineral in an organic matrix. In bone for example, OPN helps regulate the size and growth of mineral crystals [4]. During instances of pathological calcification that can occur in blood vessels (hardening of the arteries) and heart valves, OPN can behave as an inducible inhibitor of mineralization and a mediator of mineral resorption [5,6,7]. In addition, OPN is involved in the recruitment of macrophagesto sites of inflammation [2]. It can also act as a cell survival factor and protect endothelial cells from undergoingcell death (apoptosis) by binding tocell surface receptors [3]. The pro-survival effect of OPN has also been shownin other cell types, including vascular smooth muscle cells.

In biomaterials, pathologic calcification is the major cause of bioprosthetic heart valve failure. The unique ability of OPN to mitigate calcification makes it a potential therapeutic agent to limit or possibly reverse the effects of pathologic calcification in native valve tissues and bioprosthetic valve replacement materials.

References:

1. Giachelli CM, Steitz S. Osteopontin: A versatile regulator of inflammation and biomineralization. Matrix Biology 2000; 19: 615-22.
2. Giachelli CM, Lombardi D, Johnson RJ, Murry CE, Almeida M. Evidence for a role of osteopontin in macrophage infiltration in response to pathological stimuli in vivo. American Journal of Pathology 1998; 152: 353-8.
3. Scatena M, Almeida M, Chaisson ML, Fausto N, Nicosia RF, Giachelli CM. NF-kappaB mediates alphavbeta3 integrin-induced endothelial cell survival. Journal of Cell Biology 1998; 141: 1083-93.
4. Boskey AL. Osteopontin and related phosphorylated sialoproteins: Effects on mineralization. Ann N Y Acad Sci 1995; 760: 249-56.
5. Speer MY, McKee MD, Guldberg RE, Liaw L, Yang HY, Tung E, Karsenty G, Giachelli CM. Inactivation of the osteopontin gene enhances vascular calcification of matrix Gla protein-deficient mice: Evidence for osteopontin as an inducible inhibitor of vascular calcification in vivo. Journal of Experimental Medicine 2002; 196: 1047-55.
6. Steitz SA, Speer MY, McKee MD, Liaw L, Almeida M, Yang H, Giachelli CM. Osteopontin inhibits mineral deposition and promotes regression of ectopic calcification. American Journal of Pathology 2002; 161: 2035-46.
7. Ohri R, Tung E, Rajachar RM, Giachelli CM. Mitigation of ectopic calcification in osteopontin-null mice by exogenous osteopontin. Calcified Tissue International. In press.