We isolated a partial length cDNA for rat osteopontin and used it to examine its tissue specificity, its expression during bone development and its hormonal regulation. Osteopontin mRNA is most abundant in bone but is also found in considerable amounts in kidney. Osteopontin mRNA is regulated by the osteotropic hormones dexamethasone and 1,25(OH)2D 3. Estimates of osteopontin mRNA levels indicate that the osteopontin gene is turned on relatively late in calvarial development, o 1987 Academic Pr .... Inc. Osteopontin is a recently discovered non-collagenous bone matrix protein, which contains the Arg Gly Asp Ser amino acid sequence and was proposed to play a role in bone cell attachment (1,2). Osteopontin is a 44 kd acidic, sialated, phosphorylated glycoprotein, in which serine, glutamic acid/glutamine and aspartic acid/asparagine residues account for about 50% of amino acids (3,4). Osteopontin binds firmly to hydroxyapatite but its function, like that of other non-collagenous proteins, has not been established. Immunolocalization studies have demonstrated the presence of this protein in the bone matrix and in fibroblast-like cells, which may be preosteoblasts, suggesting that expression of this protein may be an early manifestation of osteoblastic differentiation (5). The object of the pilot studies presented here was to explore the potential usefulness of osteopontin as a marker of osteoblastic differentiation. Using a partial length osteopontin cDNA, we examined the distribution of osteopontin mRNA among adult rat tissues