The nature and significance of osteopontin.

Osteopontin is an acidic glycoprotein of about 41,500 daltons that has been isolated from rat, human and bovine bone. It is rich in aspartic acid, glutamic acid and serine and contains about 30 monosaccharides, including 10 sialic acids. Several types of data suggest that the carbohydrate is present as 1 N-glycoside and 5-6 O-glycosides while the phosphate is present as 12 phosphoserines and 1 phosphothreonine. The cDNA sequence indicated the presence of a Gly-Arg-Gly-Asp-Ser- (GRGDS) amino acid sequence identical to a cell binding sequence in fibronectin, and suggested that osteopontin might function as a cell attachment factor. This conclusion is supported by a number of studies showing that the protein promotes attachment and spreading of fibroblasts and osteoblasts to substratum, and that this attachment is inhibited by RGD-containing peptides. Despite this evidence that it contains an RGD recognition sequence and probably interacts with the family of receptors known as integrins, it appears that osteopontin does not possess a collagen-binding domain. Osteopontin is synthesized by preosteoblasts, osteoblasts and osteocytes, is secreted into osteoid and is incorporated into bone. The expression at an early developmental stage is an indication that osteopontin is an important component in the formation of bone. The level of synthesis of osteopontin by osteoblasts in culture is increased by treating these cells with 1,25-dihydroxyvitamin D3 and TGF-beta. The effect of these agents is at the transcriptional level. In addition to bone cells, osteopontin is synthesized by extraosseous cells in the inner ear, brain, kidney, and deciduum and placenta. It is also synthesized by odontoblasts, certain bone marrow cells and hypertrophic chondrocytes. Studies with several fibroblast and epithelial-derived cell lines in culture indicate that secretion of osteopontin can be dramatically increased when these cells are treated with phorbol esters, growth factors and hormones. However, osteopontin does not appear to be expressed by mesenchymal cells, fibroblasts, epidermal cells or by most epithelial cells in vivo.