Platelets contribute to circulating levels of bone sialoprotein in human

Bone sialoprotein (BSP) is a major bone-related protein. Although a few other tissues contain trace amounts of BSP message, bone cells and bone matrix are the major sources of BSP, suggesting that this protein could be a potential marker of bone metabolism. Purified bovine BSP showed a 70% homology of its first 13 amino acid N-terminal sequence with human BSP and was used to raise antibodies in rabbit and to develop a specific radioimmunoassay (RIA). Using this RIA, we have shown that BSP is present in serum with values in the range of 10-30 ngEq/ml in the serum of normal adults. Values obtained in plasma prepared without platelet activation are about one-half of those in matched sera, suggesting that BSP present in serum is in part derived from platelets during the activation process. Using Western blot and RIA techniques, we confirmed that platelets contain immunoreactive BSP and that the protein is released after thrombin stimulation of these cells. In addition to BSP, platelets contain a 45 kD immunoreactive material that has not been precisely identified. Available evidence indicates that this material is not osteonectin or osteopontin and that it may be a BSP-like protein rather than a degradation product of BSP. Platelets from a patient having a gray platelet syndrome, characterized by a deficiency in platelet alpha-granules and in the alpha-granule secretory proteins, did not show any deficiency of BSP, suggesting that immunoreactive BSP present in platelets is not endogenously synthesized by megakaryocytes but rather originates from plasma by endocytosis.