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The FASEB Journal, Vol 7, 1475-1482, Copyright © 1993 by The Federation of American Societies for Experimental Biology

REVIEWS

Osteopontin: a protein with diverse functions

DT Denhardt and X Guo
Department of Biological Sciences, Rutgers University, Piscataway, New Jersey 08855.

In this review most of the various known, suspected, or postulated functions of osteopontin, a secreted highly acidic phosphoprotein, are discussed in terms of what we currently know about the protein. These include 1) binding of OPN both to cells via a GRGDS cell adhesion sequence that recognizes the alpha v beta 3 integrin and to extracellular matrix components via poorly characterized motifs, 2) regulation of the formation and remodeling of mineralized tissue, 3) recruiting and stimulating macrophages and lymphocytes as part of a nonspecific response to microbial infections, 4) multiple interactions with Ca2+ that likely influence OPN protein conformation and may be important in Ca(2+)-mediated or Ca(2+)-dependent processes, 5) inhibiting the growth of calcium oxalate crystals by disruption of the growing crystal lattice, 6) effects on gene expression, Ca2+ regulation, and nitric oxide production, and 7) involvement in cell migration. OPN production is frequently augmented when cell signaling pathways are activated by any of a variety of stimuli, for example in cancer cells.


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 JEMHome page
M. Y. Speer, M. D. McKee, R. E. Guldberg, L. Liaw, H.-Y. Yang, E. Tung, G. Karsenty, and C. M. Giachelli
Inactivation of the Osteopontin Gene Enhances Vascular Calcification of Matrix Gla Protein-deficient Mice: Evidence for Osteopontin as an Inducible Inhibitor of Vascular Calcification In Vivo
J. Exp. Med., October 21, 2002; 196(8): 1047 - 1055.
[Abstract] [Full Text] [PDF]

Home page
 J. Leukoc. Biol.Home page
G. F. Weber, S. Zawaideh, S. Hikita, V. A. Kumar, H. Cantor, and S. Ashkar
Phosphorylation-dependent interaction of osteopontin with its receptors regulates macrophage migration and activation
J. Leukoc. Biol., October 1, 2002; 72(4): 752 - 761.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Endocrinol.Home page
C. M. D'Cruz, S. E. Moody, S. R. Master, J. L. Hartman, E. A. Keiper, M. B. Imielinski, J. D. Cox, J. Y. Wang, S. I. Ha, B. A. Keister, et al.
Persistent Parity-Induced Changes in Growth Factors, TGF-{beta}3, and Differentiation in the Rodent Mammary Gland
Mol. Endocrinol., September 1, 2002; 16(9): 2034 - 2051.
[Abstract] [Full Text] [PDF]

Home page
 Biol. Reprod.Home page
C. C. Luedtke, M. D. McKee, D. G. Cyr, M. Gregory, M. T. Kaartinen, J. Mui, and L. Hermo
Osteopontin Expression and Regulation in the Testis, Efferent Ducts, and Epididymis of Rats During Postnatal Development Through to Adulthood
Biol Reprod, May 1, 2002; 66(5): 1437 - 1448.
[Abstract] [Full Text]

Home page
 Infect. Immun.Home page
Y. Koguchi, K. Kawakami, S. Kon, T. Segawa, M. Maeda, T. Uede, and A. Saito
Penicillium marneffei Causes Osteopontin-Mediated Production of Interleukin-12 by Peripheral Blood Mononuclear Cells
Infect. Immun., March 1, 2002; 70(3): 1042 - 1048.
[Abstract] [Full Text] [PDF]

Home page
 Biol. Reprod.Home page
J. E. Garlow, H. Ka, G. A. Johnson, R. C. Burghardt, L. A. Jaeger, and F. W. Bazer
Analysis of Osteopontin at the Maternal-Placental Interface in Pigs
Biol Reprod, March 1, 2002; 66(3): 718 - 725.
[Abstract] [Full Text] [PDF]

Home page
 QJMHome page
M. Mazzali, T. Kipari, V. Ophascharoensuk, J.A. Wesson, R. Johnson, and J. Hughes
Osteopontin--a molecule for all seasons
QJM, January 1, 2002; 95(1): 3 - 13.
[Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
Y.-H. Lin and H.-F. Yang-Yen
The Osteopontin-CD44 Survival Signal Involves Activation of the Phosphatidylinositol 3-Kinase/Akt Signaling Pathway
J. Biol. Chem., November 30, 2001; 276(49): 46024 - 46030.
[Abstract] [Full Text] [PDF]

Home page
 ScienceHome page
D. Chabas, S. E. Baranzini, D. Mitchell, C. C. A. Bernard, S. R. Rittling, D. T. Denhardt, R. A. Sobel, C. Lock, M. Karpuj, R. Pedotti, et al.
The Influence of the Proinflammatory Cytokine, Osteopontin, on Autoimmune Demyelinating Disease
Science, November 23, 2001; 294(5547): 1731 - 1735.
[Abstract] [Full Text] [PDF]

Home page
 JEMHome page
J.M. Weiss, A.C. Renkl, C.S. Maier, M. Kimmig, L. Liaw, T. Ahrens, S. Kon, M. Maeda, H. Hotta, T. Uede, et al.
Osteopontin Is Involved in the Initiation of Cutaneous Contact Hypersensitivity by Inducing Langerhans and Dendritic Cell Migration to Lymph Nodes
J. Exp. Med., October 29, 2001; 194(9): 1219 - 1230.
[Abstract] [Full Text] [PDF]

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 J. Clin. Endocrinol. Metab.Home page
K. B. C. Apparao, M. J. Murray, M. A. Fritz, W. R. Meyer, A. F. Chambers, P. R. Truong, and B. A. Lessey
Osteopontin and Its Receptor {alpha}v{beta}3 Integrin Are Coexpressed in the Human Endometrium during the Menstrual Cycle But Regulated Differentially
J. Clin. Endocrinol. Metab., October 1, 2001; 86(10): 4991 - 5000.
[Abstract] [Full Text] [PDF]

Home page
 Biol. Reprod.Home page
G. A. Johnson, F. W. Bazer, L. A. Jaeger, H. Ka, J. E. Garlow, C. Pfarrer, T. E. Spencer, and R. C. Burghardt
Muc-1, Integrin, and Osteopontin Expression During the Implantation Cascade in Sheep
Biol Reprod, September 1, 2001; 65(3): 820 - 828.
[Abstract] [Full Text] [PDF]

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 Cancer Res.Home page
E. Medico, A. Gentile, C. L. Celso, T. A. Williams, G. Gambarotta, L. Trusolino, and P. M. Comoglio
Osteopontin Is an Autocrine Mediator of Hepatocyte Growth Factor-induced Invasive Growth
Cancer Res., August 1, 2001; 61(15): 5861 - 5868.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
M. El-Tanani, R. Barraclough, M. C. Wilkinson, and P. S. Rudland
Metastasis-inducing DNA Regulates the Expression of the Osteopontin Gene by Binding the Transcription Factor Tcf-4
Cancer Res., July 1, 2001; 61(14): 5619 - 5629.
[Abstract] [Full Text] [PDF]

Home page
 Nephrol Dial TransplantHome page
Y. Nagasawa, M. Takenaka, J. Kaimori, Y. Matsuoka, Y. Akagi, M. Tsujie, E. Imai, and M. Hori
Rapid and diverse changes of gene expression in the kidneys of protein-overload proteinuria mice detected by microarray analysis
Nephrol. Dial. Transplant., May 1, 2001; 16(5): 923 - 931.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Cell. Biol.Home page
A. Javed, G. L. Barnes, B. O. Jasanya, J. L. Stein, L. Gerstenfeld, J. B. Lian, and G. S. Stein
runt Homology Domain Transcription Factors (Runx, Cbfa, and AML) Mediate Repression of the Bone Sialoprotein Promoter: Evidence for Promoter Context-Dependent Activity of Cbfa Proteins
Mol. Cell. Biol., April 15, 2001; 21(8): 2891 - 2905.
[Abstract] [Full Text]

Home page
 Nephrol Dial TransplantHome page
W. A. Verstrepen, V. P. Persy, A. Verhulst, S. Dauwe, and M. E. De Broe
Renal osteopontin protein and mRNA upregulation during acute nephrotoxicity in the rat
Nephrol. Dial. Transplant., April 1, 2001; 16(4): 712 - 724.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Respir. Cell Mol. Bio.Home page
F. Takahashi, K. Takahashi, T. Okazaki, K. Maeda, H. Ienaga, M. Maeda, S. Kon, T. Uede, and Y. Fukuchi
Role of Osteopontin in the Pathogenesis of Bleomycin-Induced Pulmonary Fibrosis
Am. J. Respir. Cell Mol. Biol., March 1, 2001; 24(3): 264 - 271.
[Abstract] [Full Text] [PDF]

Home page
 JEMHome page
M. Ishijima, S. R. Rittling, T. Yamashita, K. Tsuji, H. Kurosawa, A. Nifuji, D. T. Denhardt, and M. Noda
Enhancement of Osteoclastic Bone Resorption and Suppression of Osteoblastic Bone Formation in Response to Reduced Mechanical Stress Do Not Occur in the Absence of Osteopontin
J. Exp. Med., February 5, 2001; 193(3): 399 - 404.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
H. Guo, C. Q. Cai, R. A. Schroeder, and P. C. Kuo
Osteopontin Is a Negative Feedback Regulator of Nitric Oxide Synthesis in Murine Macrophages
J. Immunol., January 15, 2001; 166(2): 1079 - 1086.
[Abstract] [Full Text] [PDF]

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 J. Histochem. Cytochem.Home page
A.-P. Gadeau, H. Chaulet, D. Daret, M. Kockx, J.-M. Daniel-Lamazière, and C. Desgranges
Time Course of Osteopontin, Osteocalcin, and Osteonectin Accumulation and Calcification After Acute Vessel Wall Injury
J. Histochem. Cytochem., January 1, 2001; 49(1): 79 - 86.
[Abstract] [Full Text]

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 Am. J. Physiol. Endocrinol. Metab.Home page
Y. Devaux, S. Grosjean, C. Seguin, C. David, B. Dousset, F. Zannad, C. Meistelman, N. De Talance, P.-M. Mertes, and D. Ungureanu-Longrois
Retinoic acid and host-pathogen interactions: effects on inducible nitric oxide synthase in vivo
Am J Physiol Endocrinol Metab, November 1, 2000; 279(5): E1045 - E1053.
[Abstract] [Full Text] [PDF]

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 J. Leukoc. Biol.Home page
A. W. O’Regan, J. M Hayden, and J. S. Berman
Osteopontin augments CD3-mediated interferon-{gamma} and CD40 ligand expression by T cells, which results in IL-12 production from peripheral blood mononuclear cells
J. Leukoc. Biol., October 1, 2000; 68(4): 495 - 502.
[Abstract] [Full Text]

Home page
 J. Am. Soc. Nephrol.Home page
J. M. BONVINI, U. SCHATZMANN, B. BECK-SCHIMMER, L. K. SUN, S. R. RITTLING, D. T. DENHARDT, M. LE HIR, and R. P. WÜTHRICH
Lack of In Vivo Function of Osteopontin in Experimental Anti-GBM Nephritis
J. Am. Soc. Nephrol., September 1, 2000; 11(9): 1647 - 1655.
[Abstract] [Full Text]

Home page
 Hum Mol GenetHome page
Y.-X. Zhou, X. Xu, L. Chen, C. Li, S. G. Brodie, and C.-X. Deng
A Pro250Arg substitution in mouse Fgfr1 causes increased expression of Cbfa1 and premature fusion of calvarial sutures
Hum. Mol. Genet., August 12, 2000; 9(13): 2001 - 2008.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Pathol.Home page
G. J. Nau, G. L. Chupp, J.-F. Emile, E. Jouanguy, J. S. Berman, J.-L. Casanova, and R. A. Young
Osteopontin Expression Correlates with Clinical Outcome in Patients with Mycobacterial Infection
Am. J. Pathol., July 1, 2000; 157(1): 37 - 42.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Cell. Biol.Home page
Y.-H. Lin, C.-J. Huang, J.-R. Chao, S.-T. Chen, S.-F. Lee, J. J.-Y. Yen, and H.-F. Yang-Yen
Coupling of Osteopontin and Its Cell Surface Receptor CD44 to the Cell Survival Response Elicited by Interleukin-3 or Granulocyte-Macrophage Colony-Stimulating Factor
Mol. Cell. Biol., April 15, 2000; 20(8): 2734 - 2742.
[Abstract] [Full Text]

Home page
 J. Biol. Chem.Home page
M. Nemir, D. Bhattacharyya, X. Li, K. Singh, A. B. Mukherjee, and B. B. Mukherjee
Targeted Inhibition of Osteopontin Expression in the Mammary Gland Causes Abnormal Morphogenesis and Lactation Deficiency
J. Biol. Chem., January 14, 2000; 275(2): 969 - 976.
[Abstract] [Full Text] [PDF]

Home page
 J. Exp. Biol.Home page
R. Kuykindoll, H Nishimura, D. Thomason, and S. Nishimoto
Osteopontin expression in spontaneously developed neointima in fowl (Gallus gallus)
J. Exp. Biol., January 1, 2000; 203(2): 273 - 282.
[Abstract] [PDF]

Home page
 Am. J. Physiol. Renal Physiol.Home page
H. Okada, K. Moriwaki, R. Kalluri, T. Takenaka, H. Imai, S. Ban, M. Takahama, and H. Suzuki
Osteopontin expressed by renal tubular epithelium mediates interstitial monocyte infiltration in rats
Am J Physiol Renal Physiol, January 1, 2000; 278(1): F110 - F121.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
Y. Yokosaki, N. Matsuura, T. Sasaki, I. Murakami, H. Schneider, S. Higashiyama, Y. Saitoh, M. Yamakido, Y. Taooka, and D. Sheppard
The Integrin alpha 9beta 1 Binds to a Novel Recognition Sequence (SVVYGLR) in the Thrombin-cleaved Amino-terminal Fragment of Osteopontin
J. Biol. Chem., December 17, 1999; 274(51): 36328 - 36334.
[Abstract] [Full Text] [PDF]


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