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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
Gene Review

SPP1  -  secreted phosphoprotein 1

Gallus gallus

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Disease relevance of LOC395210

  • In situ hybridization analysis of epiphyseal growth plates from chicken or mice homozygous for the Achondroplasia, G369C/mFGFR3 mutation demonstrated co-localization of OPN expression and osteoclast activity, as evidenced by tartarate resistant acid phosphatase positive cells in the osteochondral junction [1].
  • Together, these findings support a strategy designed to target osteopontin in the context of prostate cancer therapy [2].
  • Over time, osteopontin expressing dysplastic cells seemed to increase in number in high-grade PIN and increased further in adenocarcinoma, and in metastasis, almost all of the cancer cells immunohistochemically stained positive for osteopontin overexpression [2].
  • Osteopontin alterations occurred early in the disease with dysregulated expression observed in lesions of low-grade prostatic intraepithelial neoplasia (PIN) [2].
  • Our results demonstrate that osteopontin stimulates gelsolin-associated Src, leading to increased gelsolin-associated PI 3-kinase activity and PtdIns 3,4,5-P3 levels, which facilitate actin filament formation, osteoclast motility, and bone resorption [3].

High impact information on LOC395210

  • We examined the biological properties of human prostate cancer cell lines LNCaP and PC-3, in which osteopontin overexpression was achieved via lentiviral gene transduction [2].
  • Furthermore, excess osteopontin induced the LNCaP cells to acquire a strong intravasation potential in vivo in the chicken embryo chorioallantoic membrane assay for blood vessel penetration [2].
  • Mechanistically, 10 nM BAG 75 marginally slowed, but did not block, the association of bone particles with chicken osteoclasts compared with osteopontin or control media [4].
  • By contrast, other phosphoproteins similarly isolated from bone were less effective in inhibiting resorption with IC50 = 100 nM osteopontin and IC50 greater than 100 nM bone sialoprotein [4].
  • In the present study, we show that osteopontin (OPN), a proinflammatory mediator involved in tissue repair, induces IL-1beta up-regulation in human monocytes [5].

Biological context of LOC395210


Anatomical context of LOC395210

  • A cDNA clone, pCP15, specific for the chicken 66-kDa major bone phosphoprotein (osteopontin), was isolated from a subtracted library enriched in DNAs coding for mRNAs expressed in chicken differentiating chondrocytes [7].
  • Northern blot analysis of RNAs extracted from several chick embryo tissues and organs, confirm and extend the observation that osteopontin mRNA expression is not restricted to tissues involved in phosphate metabolism [7].
  • The steady state level of osteopontin mRNA was enhanced by trypsin treatment of cultured cells [7].
  • FGF upregulates osteopontin in epiphyseal growth plate chondrocytes: implications for endochondral ossification [1].
  • Inhibition of PI 3-kinase activity by wortmannin blocks osteopontin stimulation of actin filament formation, suggesting that activation of gelsolin-associated PI 3-kinase is an important pathway in cytoskeletal regulation [3].

Associations of LOC395210 with chemical compounds


Physical interactions of LOC395210

  • Our data strongly suggest that osteopontin is an osteoclast autocrine motility factor binding to avb3 and CD44 during stimulation of osteoclast migration [14].
  • We have shown that osteopontin binding to integrin alphav beta3 in osteoclasts stimulates gelsolin-associated phosphatidylinositol (PtdIns) 3-hydroxyl kinase (PI 3-kinase), leading to increased levels of gelsolin-bound PtdIns 3,4-P2, PtdIns 4,5-P2, and PtdIns 3, 4,5-P3, uncapping of barbed end actin, and actin filament formation [3].

Regulatory relationships of LOC395210


Other interactions of LOC395210


Analytical, diagnostic and therapeutic context of LOC395210


  1. FGF upregulates osteopontin in epiphyseal growth plate chondrocytes: implications for endochondral ossification. Weizmann, S., Tong, A., Reich, A., Genina, O., Yayon, A., Monsonego-Ornan, E. Matrix Biol. (2005) [Pubmed]
  2. Increased expression of osteopontin contributes to the progression of prostate cancer. Khodavirdi, A.C., Song, Z., Yang, S., Zhong, C., Wang, S., Wu, H., Pritchard, C., Nelson, P.S., Roy-Burman, P. Cancer Res. (2006) [Pubmed]
  3. c-Src is required for stimulation of gelsolin-associated phosphatidylinositol 3-kinase. Chellaiah, M., Fitzgerald, C., Alvarez, U., Hruska, K. J. Biol. Chem. (1998) [Pubmed]
  4. Bone acidic glycoprotein 75 inhibits resorption activity of isolated rat and chicken osteoclasts. Sato, M., Grasser, W., Harm, S., Fullenkamp, C., Gorski, J.P. FASEB J. (1992) [Pubmed]
  5. Cutting Edge: IL-1beta Mediates the Proangiogenic Activity of Osteopontin-Activated Human Monocytes. Naldini, A., Leali, D., Pucci, A., Morena, E., Carraro, F., Nico, B., Ribatti, D., Presta, M. J. Immunol. (2006) [Pubmed]
  6. Characterization of a cDNA for chicken osteopontin: expression during bone development, osteoblast differentiation, and tissue distribution. Moore, M.A., Gotoh, Y., Rafidi, K., Gerstenfeld, L.C. Biochemistry (1991) [Pubmed]
  7. cDNA cloning and gene expression of chicken osteopontin. Expression of osteopontin mRNA in chondrocytes is enhanced by trypsin treatment of cells. Castagnola, P., Bet, P., Quarto, R., Gennari, M., Cancedda, R. J. Biol. Chem. (1991) [Pubmed]
  8. Identification of the phosphorylated sites of metabolically 32P-labeled osteopontin from cultured chicken osteoblasts. Salih, E., Ashkar, S., Gerstenfeld, L.C., Glimcher, M.J. J. Biol. Chem. (1997) [Pubmed]
  9. Maturation-dependent thiol loss increases chondrocyte susceptibility to apoptosis. Teixeira, C.C., Rajpurohit, R., Mansfield, K., Nemelivsky, Y.V., Shapiro, I.M. J. Bone Miner. Res. (2003) [Pubmed]
  10. Recognition of osteopontin and related peptides by an alpha v beta 3 integrin stimulates immediate cell signals in osteoclasts. Miyauchi, A., Alvarez, J., Greenfield, E.M., Teti, A., Grano, M., Colucci, S., Zambonin-Zallone, A., Ross, F.P., Teitelbaum, S.L., Cheresh, D. J. Biol. Chem. (1991) [Pubmed]
  11. Engagement of the osteoclast integrin alpha v beta 3 by osteopontin stimulates phosphatidylinositol 3-hydroxyl kinase activity. Hruska, K.A., Rolnick, F., Huskey, M., Alvarez, U., Cheresh, D. Endocrinology (1995) [Pubmed]
  12. Variable hormone responsiveness of osteoblast populations isolated at different stages of embryogenesis and its relationship to the osteogenic lineage. Gerstenfeld, L.C., Zurakowski, D., Schaffer, J.L., Nichols, D.P., Toma, C.D., Broess, M., Bruder, S.P., Caplan, A.I. Endocrinology (1996) [Pubmed]
  13. Tamoxifen attenuates glucocorticoid actions on bone formation in vitro. Sukhu, B., Rotenberg, B., Binkert, C., Kohno, H., Zohar, R., McCulloch, C.A., Tenenbaum, H.C. Endocrinology (1997) [Pubmed]
  14. The integrin alpha(v)beta(3) and CD44 regulate the actions of osteopontin on osteoclast motility. Chellaiah, M.A., Hruska, K.A. Calcif. Tissue Int. (2003) [Pubmed]
  15. Comparison of two phosphoproteins in chicken bone and their similarities to the mammalian bone proteins, osteopontin and bone sialoprotein II. Gotoh, Y., Pierschbacher, M.D., Grzesiak, J.J., Gerstenfeld, L., Glimcher, M.J. Biochem. Biophys. Res. Commun. (1990) [Pubmed]
  16. Synthesis and phosphorylation of osteopontin by avian epiphyseal growth-plate chondrocytes as affected by differentiation. Barak-Shalom, T., Schickler, M., Knopov, V., Shapira, R., Hurwitz, S., Pines, M. Comp. Biochem. Physiol. C, Pharmacol. Toxicol. Endocrinol. (1995) [Pubmed]
  17. Signal transduction pathways mediating parathyroid hormone stimulation of bone sialoprotein gene expression in osteoblasts. Yang, R., Gerstenfeld, L.C. J. Biol. Chem. (1996) [Pubmed]
  18. Inhibition of Na+/Ca2+ exchange with KB-R7943 or bepridil diminished mineral deposition by osteoblasts. Stains, J.P., Gay, C.V. J. Bone Miner. Res. (2001) [Pubmed]
  19. Induction of bone-related proteins, osteocalcin and osteopontin, and their matrix ultrastructural localization with development of chondrocyte hypertrophy in vitro. Lian, J.B., McKee, M.D., Todd, A.M., Gerstenfeld, L.C. J. Cell. Biochem. (1993) [Pubmed]
  20. Osteopontin expression in spontaneously developed neointima in fowl (Gallus gallus). Kuykindoll, R.J., Nishimura, H., Thomason, D.B., Nishimoto, S.K. J. Exp. Biol. (2000) [Pubmed]
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