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Gene Review

Spp1  -  secreted phosphoprotein 1

Rattus norvegicus

Synonyms: 2b7, Bone sialoprotein 1, Osteopontin, SPP-1, Secreted phosphoprotein 1, ...
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Disease relevance of Spp1

  • Recruitment of nuclear factor Y to the inverted CCAAT element (ICE) by c-Jun and E1A stimulates basal transcription of the bone sialoprotein gene in osteosarcoma cells [1].
  • To study this question, we determined the activities of different forms of OPN and BSP in three in vitro assays: attachment of osteoclasts; formation of actin rings; and bone resorption [2].
  • Because the v-src oncogene induces expression of a number of genes that are involved in tumor growth and metastasis, including osteopontin, we have studied the effects of v-Src on transcription of the BSP gene [3].
  • Although essentially specific to mineralizing connective tissues, BSP is also expressed ectopically by carcinomas that exhibit microcalcification and which metastasize to bone with high frequency [3].
  • Altered processing of a major secreted phosphoprotein correlates with tumorigenicity in Rous sarcoma virus-transformed mammalian cells [4].

High impact information on Spp1


Chemical compound and disease context of Spp1

  • Treatment of rat osteosarcoma UMR 106 cells with 3 microm, 300 nm, and 30 nm PGE2 increased the steady state levels of BSP mRNA about 2.7-, 2.5-, and 2.4-fold after 12 h [7].
  • The present study investigates regulation of BSP transcription in rat osteosarcoma ROS 17/2.8 cells by flavonoids: genistein (an inhibitor of protein tyrosine kinases), daidzein (an inactive compound of genistein), flavone, and flavanone [8].

Biological context of Spp1


Anatomical context of Spp1

  • Bone sialoprotein (BSP), is thought to function in the initial mineralization of bone, is selectively expressed by differentiated osteoblast [9].
  • BSP was detected in osteoblasts as well as in alveolar bone matrix [13].
  • Analysis of rat bone marrow-derived osteoclasts revealed strong surface staining for CD44 and beta1- and beta3-integrins, whereas little or no staining for OPN or bone sialoprotein (BSP) was observed in nonpermeabilized cells [14].
  • Antibody raised to the Mr 62,000 rat tumor-secreted phosphoprotein was found to bind Mr 75,000 and Mr 35,000 components of human milk, indicating that milk contains antigenically related proteins [15].
  • The tissue distribution of BSP mRNA suggests that the protein may be a unique product of cells in bone tissue [16].

Associations of Spp1 with chemical compounds


Regulatory relationships of Spp1


Other interactions of Spp1


Analytical, diagnostic and therapeutic context of Spp1

  • Because PGE2 increases the proportion of functional osteoblasts in fetal rat calvarial cell cultures, we investigated the regulation of BSP, as an osteoblastic marker, by PGE2 [7].
  • Site-directed mutagenesis of the poly[E] regions in full-length BSP was performed, replacing the poly[E] with either polyaspartic acid (poly[D]) or polyalanine (poly[A]) to examine role of charge and conformation, respectively, in HA nucleation [24].
  • In this study we used Northern hybridization and in situ hybridization to determine the tissue-specific and developmental expression of BSP during embryogenesis and growth of rat tissues [25].
  • Semiquantitative reverse transcriptase polymerase chain reaction assays of BSP mRNA revealed increases of 7-, 74-, and 66-fold, respectively, in the same rachitic bones, while OPN mRNA was reduced 12.5-fold in calvariae and 2-fold in tibiae and mandibles [26].
  • Avidin affinity purification of bone extract labeled with biotinylated primary amine in the presence of tTG, in conjunction with Western blotting, permitted identification of three major noncollagenous TG substrates in bone: osteopontin (OPN), bone sialoprotein (BSP), and alpha2 HS-glycoprotein (AHSG), of which the latter two are novel substrates [27].


  1. Recruitment of nuclear factor Y to the inverted CCAAT element (ICE) by c-Jun and E1A stimulates basal transcription of the bone sialoprotein gene in osteosarcoma cells. Su, M., Bansal, A.K., Mantovani, R., Sodek, J. J. Biol. Chem. (2005) [Pubmed]
  2. Osteopontin posttranslational modifications, possibly phosphorylation, are required for in vitro bone resorption but not osteoclast adhesion. Razzouk, S., Brunn, J.C., Qin, C., Tye, C.E., Goldberg, H.A., Butler, W.T. Bone (2002) [Pubmed]
  3. Transcription of the bone sialoprotein gene is stimulated by v-Src acting through an inverted CCAAT box. Kim, R.H., Sodek, J. Cancer Res. (1999) [Pubmed]
  4. Altered processing of a major secreted phosphoprotein correlates with tumorigenicity in Rous sarcoma virus-transformed mammalian cells. Chackalaparampil, I., Banerjee, D., Poirier, Y., Mukherjee, B.B. J. Virol. (1985) [Pubmed]
  5. Transcriptional regulation of osteopontin production in rat osteoblast-like cells by parathyroid hormone. Noda, M., Rodan, G.A. J. Cell Biol. (1989) [Pubmed]
  6. Regulation of bone sialoprotein mRNA by steroid hormones. Oldberg, A., Jirskog-Hed, B., Axelsson, S., Heinegård, D. J. Cell Biol. (1989) [Pubmed]
  7. Prostaglandin E2 stimulates bone sialoprotein (BSP) expression through cAMP and fibroblast growth factor 2 response elements in the proximal promoter of the rat BSP gene. Samoto, H., Shimizu, E., Matsuda-Honjyo, Y., Saito, R., Nakao, S., Yamazaki, M., Furuyama, S., Sugiya, H., Sodek, J., Ogata, Y. J. Biol. Chem. (2003) [Pubmed]
  8. Activation of bone sialoprotein gene transcription by flavonoids is mediated through an inverted CCAAT box in ROS 17/2.8 cells. Shimizu, E., Ogata, Y. J. Cell. Biochem. (2002) [Pubmed]
  9. Insulin-like growth factor-I increases bone sialoprotein (BSP) expression through fibroblast growth factor-2 response element and homeodomain protein-binding site in the proximal promoter of the BSP gene. Nakayama, Y., Nakajima, Y., Kato, N., Takai, H., Kim, D.S., Arai, M., Mezawa, M., Araki, S., Sodek, J., Ogata, Y. J. Cell. Physiol. (2006) [Pubmed]
  10. Fibroblast growth factor 2 and cyclic AMP synergistically regulate bone sialoprotein gene expression. Shimizu, E., Nakayama, Y., Nakajima, Y., Kato, N., Takai, H., Kim, D.S., Arai, M., Saito, R., Sodek, J., Ogata, Y. Bone (2006) [Pubmed]
  11. AP-1 regulation of the rat bone sialoprotein gene transcription is mediated through a TPA response element within a glucocorticoid response unit in the gene promoter. Yamauchi, M., Ogata, Y., Kim, R.H., Li, J.J., Freedman, L.P., Sodek, J. Matrix Biol. (1996) [Pubmed]
  12. In vitro and in vivo effects of the overexpression of osteopontin on osteoblast differentiation using a recombinant adenoviral vector. Kojima, H., Uede, T., Uemura, T. J. Biochem. (2004) [Pubmed]
  13. Immunohistochemical Localization of {alpha}-Smooth Muscle Actin During Rat Molar Tooth Development. Hosoya, A., Nakamura, H., Ninomiya, T., Yoshiba, K., Yoshiba, N., Nakaya, H., Wakitani, S., Yamada, H., Kasahara, E., Ozawa, H. J. Histochem. Cytochem. (2006) [Pubmed]
  14. Colocalization of intracellular osteopontin with CD44 is associated with migration, cell fusion, and resorption in osteoclasts. Suzuki, K., Zhu, B., Rittling, S.R., Denhardt, D.T., Goldberg, H.A., McCulloch, C.A., Sodek, J. J. Bone Miner. Res. (2002) [Pubmed]
  15. Purification of a human milk protein closely similar to tumor-secreted phosphoproteins and osteopontin. Senger, D.R., Perruzzi, C.A., Papadopoulos, A., Tenen, D.G. Biochim. Biophys. Acta (1989) [Pubmed]
  16. The primary structure of a cell-binding bone sialoprotein. Oldberg, A., Franzén, A., Heinegård, D. J. Biol. Chem. (1988) [Pubmed]
  17. Cloning and sequence analysis of rat bone sialoprotein (osteopontin) cDNA reveals an Arg-Gly-Asp cell-binding sequence. Oldberg, A., Franzén, A., Heinegård, D. Proc. Natl. Acad. Sci. U.S.A. (1986) [Pubmed]
  18. Synthesis and processing of bone sialoproteins during de novo bone formation in vitro. Zhu, X.L., Ganss, B., Goldberg, H.A., Sodek, J. Biochem. Cell Biol. (2001) [Pubmed]
  19. TNF-alpha suppresses bone sialoprotein (BSP) expression in ROS17/2.8 cells. Samoto, H., Shimizu, E., Matsuda-Honjo, Y., Saito, R., Yamazaki, M., Kasai, K., Furuyama, S., Sugiya, H., Sodek, J., Ogata, Y. J. Cell. Biochem. (2002) [Pubmed]
  20. Regulation of mRNA expression of matrix extracellular phosphoglycoprotein (MEPE)/ osteoblast/osteocyte factor 45 (OF45) by fibroblast growth factor 2 in cultures of rat bone marrow-derived osteoblastic cells. Zhang, G.X., Mizuno, M., Tsuji, K., Tamura, M. Endocrine (2004) [Pubmed]
  21. Nucleobindin is produced by bone cells and secreted into the osteoid, with a potential role as a modulator of matrix maturation. Petersson, U., Somogyi, E., Reinholt, F.P., Karlsson, T., Sugars, R.V., Wendel, M. Bone (2004) [Pubmed]
  22. Nell-1 induced bone formation within the distracted intermaxillary suture. Cowan, C.M., Cheng, S., Ting, K., Soo, C., Walder, B., Wu, B., Kuroda, S., Zhang, X. Bone (2006) [Pubmed]
  23. Sequential expression of matrix protein genes in developing rat teeth. Bleicher, F., Couble, M.L., Farges, J.C., Couble, P., Magloire, H. Matrix Biol. (1999) [Pubmed]
  24. Delineation of the hydroxyapatite-nucleating domains of bone sialoprotein. Tye, C.E., Rattray, K.R., Warner, K.J., Gordon, J.A., Sodek, J., Hunter, G.K., Goldberg, H.A. J. Biol. Chem. (2003) [Pubmed]
  25. Development expression of bone sialoprotein mRNA in rat mineralized connective tissues. Chen, J., Shapiro, H.S., Sodek, J. J. Bone Miner. Res. (1992) [Pubmed]
  26. Altered expression of bone sialoproteins in vitamin D-deficient rBSP2.7Luc transgenic mice. Chen, J.J., Jin, H., Ranly, D.M., Sodek, J., Boyan, B.D. J. Bone Miner. Res. (1999) [Pubmed]
  27. Tissue transglutaminase and its substrates in bone. Kaartinen, M.T., El-Maadawy, S., Räsänen, N.H., McKee, M.D. J. Bone Miner. Res. (2002) [Pubmed]
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