Alternative titles; symbols
HGNC Approved Gene Symbol: SPP1
Cytogenetic location: 4q22.1 Genomic coordinates (GRCh38): 4:87,975,714-87,983,411 (from NCBI)
SPP1 belongs to the small integrin-binding ligand N-linked glycoprotein (SIBLING) family of secreted phosphoproteins. SIBLINGs are involved in bone mineralization (summary by Ogbureke and Fisher, 2007).
Kiefer et al. (1989) presented the cDNA and derived amino acid sequence of osteopontin. Young et al. (1990) showed that the deduced protein sequence shows a conservation in the cell attachment site arg-gly-asp. Northern analysis showed that osteopontin mRNA was predominant in cultures of bone cells and in the decidua of a placenta isolated at 8 to 12 weeks of gestation.
Kohri et al. (1992) sequenced a cDNA of urinary stone protein, the proteinaceous matrix of urinary stones. The sequence showed complete homology with that of osteopontin. Furthermore, Kohri et al. (1993) showed that urinary calcium oxalate stones consist of osteopontin protein. By means of in situ hybridization, they demonstrated osteopontin mRNA in the kidney, specifically in the distal tubular cells. In a rat model of stone formation induced with glyoxylic acid, they found that staining for osteopontin was remarkably increased in distal tubular cells, whereas proximal tubular cells and glomeruli remained negative as in the normal kidney.
Using RT-PCR, Ogbureke and Fisher (2005) found that osteopontin was expressed in normal adult human kidney. Immunohistochemical analysis and in situ hybridization of monkey kidney revealed that osteopontin expression was restricted to distal convoluted tubules and distal straight tubules in cortex and medulla.
By immunohistochemical analysis, Ogbureke and Fisher (2007) found that OPN colocalized with MMP3 (185250) in cells of human secretory and excretory eccrine sweat glands, with strongest staining in perinuclear regions. Other members of the SIBLING family also colocalized with specific metalloproteinase partners. Neither OPN nor MMP2 were detected in connective tissue cells and stroma of human eccrine sweat gland or in acini and ducts of monkey lacrimal gland.
Shinohara et al. (2008) found that mouse Opn mRNA contains 2 translational start sites and produces a full-length protein with a signal peptide and a short protein that lacks the signal peptide. Western blot analysis detected 70- and 75-kD Opn proteins in mouse plasmacytoid and conventional dendritic cells (DCs). Immunofluorescence and biochemical analyses of transfected HEK293FT cells and endogenous proteins in mouse DCs showed that the short Opn isoform localized mainly to cytoplasm, whereas the full-length Opn isoform localized to secretory vesicles and Golgi.
In the 19th century Kolliker gave the name 'Osteoklast' to a large multinucleated cell observed along bone surfaces and suggested a role for the cell in bone resorption. It is now known that osteoclasts are derived from a bone-marrow cell reaching the surface of the bone by means of blood-borne mononuclear precursor cells. Osteopontin, a protein that is produced by osteoblasts under stimulation by calcitriol and binds tightly to hydroxyapatite, was shown by Reinholt et al. (1990) to be involved in the anchoring of osteoclasts to the mineral of bone matrix. Vitronectin receptor (193210), which has specificity for osteopontin, is preferentially located in the area of the osteoclast plasma membrane involved in the binding process.
The 1-alpha-1,25-dihydroxyvitamin D3 (VD3)-dependent stimulation of the osteopontin (OPN) gene transcription in bone tissue is mediated by interactions of trans-activating factors with distinct VD3-responsive elements (VDREs). To determine the identity of endogenous VD3-induced complexes recognizing the OPN-VDREs in osteoblasts, Staal et al. (1996) performed gel shift immunoassays with nuclear proteins from osteoblastic cells using a panel of monoclonal antibodies. They showed that VD3-inducible complexes interacting with the OPN-VDREs represent 2 distinct heterodimeric complexes, each composed of the vitamin D receptor (VDR) and the retinoid X receptor-alpha (RXR). The OPN-VDR/RXR-alpha heterodimers are immunoreactive with RXR antibodies and several antibodies directed against the ligand-binding domain of the VDR. The OPN-VDR/RXR-alpha complexes may reflect specialized requirements for VD3 regulation of the OPN gene expression in response to physiologic cues mediating osteoblast differentiation.
Baccarani-Contri et al. (1995) demonstrated that osteopontin is a constitutive component of normal elastic fibers in human skin and aorta. Antibodies raised against human bone osteopontin or against osteopontin synthetic peptide (amino acids 1-10) recognized epitopes associated with the amorphous material within elastic fibers. Elastic fiber-associated microfibrils were always negative. A positivity for osteopontin of the elastic fibers was independent of age and could be observed in fetal skin and aorta as well as in those of children, young adults, and old subjects. The presence of osteopontin within elastic fibers suggested to them that it may play a role in relation to the observed tendency of elastic fibers to undergo mineral precipitation. A role of osteopontin in modulating crystal nucleation and growth in mineralizing tissues and, more generally, in conditions in which mineral precipitation should be controlled is possible.
Osteopontin is also termed Eta-1, for 'early T lymphocyte activation 1.' Weber et al. (1996) found that osteopontin is a protein ligand of CD44 (107269).
Beck et al. (2000) reported results specifically linking induction of osteopontin to the enzymatic activity of alkaline phosphatase in culture medium, which resulted in the generation of free phosphate. The elevation of free phosphate in the medium was sufficient to signal induction of osteopontin RNA and protein. The strong and specific induction of osteopontin in direct response to increased phosphate levels provided a mechanism to explain how its expression is normally regulated in bone, as well as how it may become upregulated in damaged tissue.
Two genes, TAP1 (170260) and SCYD1 (encoding fractalkine; 601880), may contribute to suppress tumor growth through host immunosurveillance. These genes were identified as downstream targets of the TP53 tumor suppressor gene (191170). As noted by Ashkar et al. (2000), osteopontin is one of the key cytokines for type 1 immune responses mediated by macrophages in mice. Osteopontin may also play a role in suppressing tumor growth in vivo. Morimoto et al. (2002) identified the OPN gene as a TP53 target gene and found that its expression was upregulated by DNA damage-induced TP53 activity and by adenovirus-mediated transfer of the human TP53 gene. They demonstrated that the OPN gene has a functional TP53-responsive element in its promoter region and confirmed an interaction between the OPN promoter and Tp53 protein in vivo. The results suggested that OPN is a direct transcriptional target of TP53. The TP53-directed regulation of OPN expression suggested a novel mechanism of TP53 participation in immunosurveillance, involving interaction with the host immune system to prevent damaged cells from undergoing malignant transformation.
Kim et al. (2002) performed validation studies of the upregulated gene osteopontin, previously identified in ovarian cancer using a cDNA microarray system. The studies provided evidence for an association between levels of this biomarker and ovarian cancer and suggested that future research assessing its clinical usefulness would be worthwhile.
Kim et al. (2003) found that human FGF2 (134920) induced osteopontin expression and cranial suture closure in mouse calvaria organ cultures. In mouse cells, FGF2 indirectly induced osteopontin expression by upregulating expression of Fos (164810)- and Jun (165160)-related genes encoding activator protein-1 (AP1) subunits, and AP1 induced osteopontin expression via an AP1 response element in the osteopontin promoter. Blocking the ERK pathway (see 601795) suppressed FGF2-stimulated AP1 and osteopontin expression and retarded FGF2-accelerated cranial suture closure.
Using RT-PCR and ELISA, Shinohara et al. (2005) observed reduced Opn expression in Tbet (TBX21; 604895) -/- mouse T cells, but not in Tbet -/- macrophages. Activated Opn -/- T cells expressed a substantially lower ratio of Ifng (147570) to Il10 (124092) and less Il12 (see 161560) compared with wildtype T cells, whereas development of experimental autoimmune encephalitis was blunted in Opn -/- mice. Shinohara et al. (2005) suggested that OPN expression is essential for promotion of robust Th1 responses.
Shinohara et al. (2006) found that engagement of Tlr9 (605474) induced expression of Opn in mouse plasmacytoid DCs, but not conventional DCs, in a Tbet-dependent manner. Studies of Opn-deficient and reconstituted plasmacytoid DCs showed that intracellular expression of Opn was required for Tlr9-dependent expression of Ifna (147660), but not other proinflammatory cytokines. Confocal microscopy demonstrated coexpression of Opn, Tlr9, and Myd88 (602170) following Tlr9 stimulation. Mice lacking Opn developed impaired Ifna-dependent natural killer (NK) cell responses to tumors and reduced Ifna responses after infection with herpes simplex virus-1.
Shinohara et al. (2008) found that the short, intracellular isoform of mouse Opn activated expression of an IFNA4 (147564) promoter reporter in transfected HEK293FT cells and podosome formation in mouse plasmacytoid DCs. They proposed that factors that alter the translational balance of Opn in favor of either full-length Opn or the short Opn isoform may contribute to the phenotype of activated DCs.
Tagliabracci et al. (2012) determined that the SIBLING family of secreted phosphoproteins are phosphorylated by FAM20C (611061), the Golgi casein kinase that phosphorylates secretory pathway proteins with S-x-E motifs. SIBLINGs are secretory calcium-binding phosphoproteins encoded by 5 identically oriented tandem genes clustered within an approximately 375-kb span of nucleotides on human chromosome 4. The genes encode osteopontin (OPN), dentin matrix protein-1 (DMP1; 600980), bone sialoprotein (IBSP; 147563), matrix extracellular phosphoglycoprotein (MEPE; 605912), and dentin sialophosphoprotein (DSPP; 125485). The SIBLINGs are highly phosphorylated proteins (DSPP has approximately 200 phosphoserines) and contain multiple phosphorylated S-x-E/S motifs.
Young et al. (1990) determined that the SPP1 gene is present in single copy with an approximate length of 5.4 to 8.2 kb.
Crosby et al. (1995) showed that the SPP1 gene comprises 7 exons, 6 of which contain coding sequence.
By means of human-rodent cell hybrids, Young et al. (1990) assigned the OPN gene to chromosome 4. A high frequency BglII RFLP was demonstrated. Fisher et al. (1990) assigned this gene to chromosome 4 by Southern analysis of somatic cell hybrids. Crosby et al. (1996) assigned the SPP1 gene to 4q21-q25 in the human (by analysis of somatic cell hybrids with various deletions of that chromosome) and to mouse chromosome 5. SPP1 and IBSP (147563) are closely linked in human and mouse and Crosby et al. (1996) found from analysis of YAC libraries that they are separated by a maximum of 340 kb. The 2 proteins share a number of physical and chemical properties, although SPP1 has a much wider tissue distribution than does IBSP, being synthesized by a range of non-mineralizing tissues, including the inner ear and kidney.
Osteopontin is the principal phosphorylated glycoprotein of bone and is expressed in a limited number of other tissues including dentin. Crosby et al. (1995) found that a highly informative short tandem repeat (STR) polymorphism located at the SPP1 locus showed no recombination with the autosomal dominant disorder dentinogenesis imperfecta type II (125490). Nonetheless, sequencing of each exon in individuals affected by this disorder failed to reveal any disease-specific mutations.
Singh et al. (1995) identified osteopontin in cultured rat cardiomyocytes. Graf et al. (1997) used tissue in situ hybridization to localize osteopontin mRNA in cardiac muscle specimens. Osteopontin mRNA was undetectable in both normal adult mouse hearts and histologically normal human right ventricular endomyocardial biopsy material. In contrast, mRNA was localized to the cytoplasm of cardiomyocytes in hypertrophied muscle taken from aortic banded or hypertensive mice and from explanted human hearts with either idiopathic or ischemic cardiomyopathy. Based on these findings, Graf et al. (1997) suggested that osteopontin is involved in the regulation of cardiac remodeling.
Liaw et al. (1998) generated osteopontin null mutant mice by targeted mutagenesis in embryonic stem cells. In these mice, embryogenesis occurred normally, and mice were fertile. Since osteopontin shares receptors with vitronectin (193190), Liaw et al. (1998) tested for compensation by creating mice lacking both proteins. The double mutants were also viable, suggesting that other arginine-glycine-aspartate (RGD)-containing ligands replaced the embryonic loss of both proteins. They tested the healing of skin incisions in the osteopontin mutants. The spp1 gene was upregulated as early as 6 hours after wounding. Although the tensile properties of the wounds were unchanged, ultrastructural analysis showed a significantly decreased level of debridement, greater disorganization of matrix, and an alteration of collagen fibrillogenesis leading to small diameter collagen fibrils in the osteopontin-mutant mice. These data indicated a role for osteopontin in tissue remodeling in vivo, and suggested physiologic functions during matrix reorganization after injury.
Yoshitake et al. (1999) reported that osteopontin knockout mice are resistant to ovariectomy-induced bone resorption compared with wildtype mice. Microcomputed tomography analysis indicated about 60% reduction in bone volume by ovariectomy in wildtype mice, whereas the osteopontin-deficient mice exhibited only about 10% reduction in trabecular bone volume after ovariectomy. Reduction in uterine weight was observed similarly in both wildtype and osteopontin-deficient mice, indicating the specificity of the effect of osteopontin deficiency on bone metabolism. Yoshitake et al. (1999) proposed that osteopontin is essential for postmenopausal osteoporosis in women. Strategies to counteract osteopontin's action may prove effective in suppressing osteoporosis.
Ashkar et al. (2000) reported that mice deficient in osteopontin gene expression have severely impaired type 1 immunity to viral infection and bacterial infection and do not develop sarcoid-type granulomas. IL12 and IFNG production is diminished, and IL10 production is increased. A phosphorylation-dependent interaction between the amino-terminal portion of osteopontin and its integrin receptor stimulated IL12 expression, whereas phosphorylation-independent interaction with CD44 inhibited IL10 expression. Ashkar et al. (2000) concluded that osteopontin is a key cytokine that sets the stage for efficient type 1 immune responses through differential regulation of macrophage IL12 and IL10 cytokine expression.
Chabas et al. (2001) identified an abundance of transcripts for osteopontin in brains of patients with multiple sclerosis (126200), whereas none was detected in control brains. Microarray analysis of spinal cords from rats paralyzed by experimental autoimmune encephalomyelitis, a model of MS, also revealed increased OPN transcripts. Chabas et al. (2001) found that osteopontin-deficient mice were resistant to progressive experimental autoimmune encephalomyelitis and had frequent remissions, and myelin-reactive T cells in Opn -/- mice produced more IL10 and less interferon-gamma than Opn +/+ mice. Chabas et al. (2001) concluded that osteopontin appears to regulate T helper cell-1 (TH1)-mediated demyelinating disease, and may offer a potential target in blocking development of progressive MS.
Blom et al. (2003) deleted the Opn gene using homologous recombination of strain 129-derived cells, and subsequently backcrossed it to the C57/BL10 strain with a congenic major histocompatibility complex fragment of the q haplotype (B10.Q), which is usually susceptible to experimental autoimmune encephalomyelitis, collagen-induced arthritis, and anti-CII antibody transfer-induced arthritis. The gene was shown to be completely inactivated. The mice were backcrossed for 12 generations; in all experiments, both wildtype B10.Q littermates and heterozygous littermates were used as controls. In contrast to the findings published by Chabas et al. (2001), Blom et al. (2003) saw no effect on any inflammatory model tested. Blom et al. (2003) suggested that the results observed by Chabas et al. (2001) may be explained by polymorphic genes linked to the Opn locus. Steinman et al. (2003), responding to the comments of Blom et al. (2003), reported that vaccination against OPN potently modulates experimental autoimmune encephalomyelitis and suggested that the divergent results described by Blom et al. (2003) may be due to differences between the experimental autoimmune encephalomyelitis model that they studied and the model used by Chabas et al. (2001).
Using rat aortic smooth muscle cells, Renault et al. (2003) demonstrated that UTP-induced OPN mRNA increased via both OPN mRNA stabilization and OPN promoter activation. Within the rat OPN promoter, they located a UTP-activated promoter element from nucleotides -96 to +1, which mediated UTP-induced OPN overexpression. Sequence analysis revealed a potential site for activator protein-1 (AP1; see 165160) at position -76. Deletion of this site totally inhibited UTP-induced activation of the -96 to +1 region, showing that this AP1 site is involved in UTP-induced OPN transcription. A supershift assay revealed that both c-fos (see 164810) and c-jun bind to this AP1 site. Renault et al. (2003) also demonstrated that angiotensin II (see 106150) and platelet-derived growth factor (see 173490), 2 main factors involved in vessel wall pathology, modulated OPN expression via AP1 activation.
In a mouse model of rheumatoid arthritis (180300), Yamamoto et al. (2003) demonstrated that M5 antibody, which specifically recognizes a cryptic epitope (SLAYGLR) exposed by thrombin cleavage of mouse Opn, could abrogate monocyte migration toward the thrombin-cleaved form of Opn. M5 antibody also inhibited the proliferation of synovium, bone erosion, and inflammatory cell infiltration in arthritic joints. Yamamoto et al. (2003) concluded that the cryptic mouse Opn epitope SLAYGLR is critically involved in the pathogenesis of a mouse model of rheumatoid arthritis.
Several proteins that are involved in the regulation of skeletal bone formation are also found in atherosclerotic lesions, including matrix Gla protein (MGP; 154870) and OPN. OPN is abundantly expressed in calcified arteries, but is absent in normal soft tissue and blood vessels. Speer et al. (2002) generated mice deficient in Mgp and/or Opn. There was no embryologic lethality, but Mgp -/- Opn -/-, Mgp -/- Opn +/-, Mgp -/- Opn +/+, and Mgp +/- Opn -/- mice started to die 3 to 4 weeks after birth due to vascular rupture and hemorrhage, most likely because of severe vascular calcification. Immunohistochemical analysis demonstrated that Opn coated mineral deposits and colocalized to cells of the calcifying medial layer in Mgp -/- Opn +/+ mice, but not wildtype mice. Cells synthesizing Opn lacked smooth muscle cell markers, but most were not macrophages. Mgp -/- Opn -/- mice had twice as much arterial calcification at 2 weeks and 3 times as much at 4 weeks as did Mgp -/- Opn +/+ mice, and they died significantly earlier. Speer et al. (2002) concluded that OPN is an inducible inhibitor of ectopic calcification in vivo.
Diao et al. (2004) examined a functional link between OPN and natural killer T (NKT) cells using a mouse model of mitogen-induced hepatitis. They found that NKT cells secreted Opn, which activated NKT cells and triggered neutrophil infiltration and activation. Mice lacking Opn or NKT cells did not develop hepatitis upon mitogen challenge. Antibody to a cryptic epitope of Opn, SLAYGLR (SVVYGLR in humans), inhibited migration of liver-infiltrating cells and interaction of Opn with alpha/beta integrin molecules and reduced serum ALT levels and liver necrosis. Diao et al. (2004) proposed that targeting of the SVVYGLR epitope of OPN may be useful in the treatment of inflammatory hepatitis.
Abel et al. (2005) found that Opn -/- and wildtype mice challenged with either influenza or vaccinia virus showed no differences in terms of viral clearance, lung inflammation, and recruitment of effector T cells to the lung. Likewise, but contrary to the findings of Ashkar et al. (2000), control of bacterial burden following Listeria monocytogenes infection was normal in Opn -/- mice. Abel et al. (2005) concluded that OPN is dispensable for antiviral and antilisterial immunity.
Nomiyama et al. (2007) exposed mice to a high-fat diet and observed increased plasma Opn levels, with elevated expression in macrophages recruited into adipose tissue. Obese Opn-null mice displayed improved insulin sensitivity in the absence of an effect on diet-induced obesity, body composition, or energy expenditure, and showed decreased macrophage infiltration into adipose tissue. In addition, obese Opn-null mice exhibited decreased markers of inflammation, both in adipose tissue and systemically. Nomiyama et al. (2007) suggested that OPN may play a key role in linking obesity to the development of insulin resistance by promoting inflammation and the accumulation of macrophages in adipose tissue.
Rittling et al. (2009) observed more severe periapical bone loss and increased inflammation associated with endodontic infection in Opn -/- mice compared with wildtype mice. Early after infection, Opn -/- mice exhibited increased Il1a (147760) and Rankl (TNFSF11; 602642) expression and slightly increased neutrophil infiltration, but they showed no change in the adaptive immune response. Rittling et al. (2009) concluded that OPN has a protective effect on polymicrobial infection.
Abel, B., Freigang, S., Bachmann, M. F., Boschert, U., Kopf, M. Osteopontin is not required for the development of Th1 responses and viral immunity. J. Immun. 175: 6006-6013, 2005. [PubMed: 16237095] [Full Text: https://doi.org/10.4049/jimmunol.175.9.6006]
Ashkar, S., Weber, G. F., Panoutsakopoulou, V., Sanchirico, M. E., Jansson, M., Zawaideh, S., Rittling, S. R., Denhardt, D. T., Glimcher, M. J., Cantor, H. Eta-1 (osteopontin): an early component of type-1 (cell-mediated) immunity. Science 287: 860-864, 2000. [PubMed: 10657301] [Full Text: https://doi.org/10.1126/science.287.5454.860]
Baccarani-Contri, M., Taparelli, F., Pasquali-Ronchetti, I. Osteopontin is a constitutive component of normal elastic fibers in human skin and aorta. Matrix Biol. 14: 553-560, 1995. [PubMed: 8535605] [Full Text: https://doi.org/10.1016/s0945-053x(05)80004-6]
Beck, G. R., Jr., Zerler, B., Moran, E. Phosphate is a specific signal for induction of osteopontin gene expression. Proc. Nat. Acad. Sci. 97: 8352-8357, 2000. [PubMed: 10890885] [Full Text: https://doi.org/10.1073/pnas.140021997]
Blom, T., Franzen, A., Heinegard, D., Holmdahl, R. Comment on 'The influence of the proinflammatory cytokine, osteopontin, on autoimmune demyelinating disease.' Science 299: 1845, 2003. [PubMed: 12649465] [Full Text: https://doi.org/10.1126/science.1080223]
Chabas, D., Baranzini, S. E., Mitchell, D., Bernard, C. C. A., Rittling, S. R., Denhardt, D. T., Sobel, R. A., Lock, C., Karpuj, M., Pedotti, R., Heller, R., Oksenberg, J. R., Steinman, L. The influence of the proinflammatory cytokine, osteopontin, on autoimmune demyelinating disease. Science 294: 1731-1735, 2001. [PubMed: 11721059] [Full Text: https://doi.org/10.1126/science.1062960]
Crosby, A. H., Edwards, S. J., Murray, J. C., Dixon, M. J. Genomic organization of the human osteopontin gene: exclusion of the locus from a causative role in the pathogenesis of dentinogenesis imperfecta type II. Genomics 27: 155-160, 1995. [PubMed: 7665163] [Full Text: https://doi.org/10.1006/geno.1995.1018]
Crosby, A. H., Lyu, M. S., Lin, K., McBride, O. W., Kerr, J. M., Aplin, H. M., Fisher, L. W., Young, M. F., Kozak, C. A., Dixon, M. J. Mapping of the human and mouse bone sialoprotein and osteopontin loci. Mammalian Genome 7: 149-151, 1996. [PubMed: 8835534] [Full Text: https://doi.org/10.1007/s003359900037]
Diao, H., Kon, S., Iwabuchi, K., Kimura, C., Morimoto, J., Ito, D., Segawa, T., Maeda, M., Hamuro, J., Nakayama, T., Taniguchi, M., Yagita, H., Van Kaer, L., Onoe, K., Denhardt, D., Rittling, S., Uede, T. Osteopontin as a mediator of NKT cell function in T cell-mediated liver diseases. Immunity 21: 539-550, 2004. [PubMed: 15485631] [Full Text: https://doi.org/10.1016/j.immuni.2004.08.012]
Fisher, L. W., McBride, O. W., Termine, J. D., Young, M. F. Human bone sialoprotein: deduced protein sequence and chromosomal localization. J. Biol. Chem. 265: 2347-2351, 1990. [PubMed: 2404984]
Graf, K., Do, Y. S., Ashizawa, N., Meehan, W. P., Giachelli, C. M., Marboe, C. C., Fleck, E., Hsueh, W. A. Myocardial osteopontin expression is associated with left ventricular hypertrophy. Circulation 96: 3063-3071, 1997. [PubMed: 9386176] [Full Text: https://doi.org/10.1161/01.cir.96.9.3063]
Kiefer, M. C., Bauer, D. M., Barr, P. J. The cDNA and derived amino acid sequence for human osteopontin. Nucleic Acids Res. 17: 3306, 1989. [PubMed: 2726470] [Full Text: https://doi.org/10.1093/nar/17.8.3306]
Kim, H.-J., Lee, M.-H., Park, H.-S., Park, M.-H., Lee, S.-W., Kim, S.-Y., Choi, J.-Y., Shin, H.-I., Kim, H.-J., Ryoo, H.-M. Erk pathway and activator protein 1 play crucial roles in FGF2-stimulated premature cranial suture closure. Dev. Dyn. 227: 335-346, 2003. [PubMed: 12815619] [Full Text: https://doi.org/10.1002/dvdy.10319]
Kim, J.-H., Skates, S. J., Uede, T., Wong, K., Schorge, J. O., Feltmate, C. M., Berkowitz, R. S., Cramer, D. W., Mok, S. C. Osteopontin as a potential diagnostic biomarker for ovarian cancer. JAMA 287: 1671-1679, 2002. [PubMed: 11926891] [Full Text: https://doi.org/10.1001/jama.287.13.1671]
Kohri, K., Nomura, S., Kitamura, Y., Nagata, T., Yoshioka, K., Iguchi, M., Yamate, T., Umekawa, T., Suzuki, Y., Sinohara, H., Kurita, T. Structure and expression of the mRNA encoding urinary stone protein (osteopontin). J. Biol. Chem. 268: 15180-15184, 1993. [PubMed: 8325891]
Kohri, K., Suzuki, Y., Yoshida, K., Yamamoto, K., Amasaki, N., Yamate, T., Umekawa, T., Iguchi, M., Sinohara, H., Kurita, T. Molecular cloning and sequencing of cDNA encoding urinary stone protein, which is identical to osteopontin. Biochem. Biophys. Res. Commun. 184: 859-864, 1992. [PubMed: 1575754] [Full Text: https://doi.org/10.1016/0006-291x(92)90669-c]
Liaw, L., Birk, D. E., Ballas, C. B., Whitsitt, J. S., Davidson, J. M., Hogan, B. L. M. Altered wound healing in mice lacking a functional osteopontin gene (spp1). J. Clin. Invest. 101: 1468-1478, 1998. [PubMed: 9525990] [Full Text: https://doi.org/10.1172/JCI2131]
Morimoto, I., Sasaki, Y., Ishida, S., Imai, K., Tokino, T. Identification of the osteopontin gene as a direct target of TP53. Genes Chromosomes Cancer 33: 270-278, 2002. [PubMed: 11807984] [Full Text: https://doi.org/10.1002/gcc.10020]
Nomiyama, T., Perez-Tilve, D., Ogawa, D., Gizard, F., Zhao, Y., Heywood, E. B., Jones, K. L., Kawamori, R., Cassis, L. A., Tschop, M. H., Bruemmer, D. Osteopontin mediates obesity-induced adipose tissue macrophage infiltration and insulin resistance in mice. J. Clin. Invest. 117: 2877-2888, 2007. [PubMed: 17823662] [Full Text: https://doi.org/10.1172/JCI31986]
Ogbureke, K. U. E., Fisher, L. W. Renal expression of SIBLING proteins and their partner matrix metalloproteinases (MMPs). Kidney Int. 68: 155-166, 2005. [PubMed: 15954904] [Full Text: https://doi.org/10.1111/j.1523-1755.2005.00389.x]
Ogbureke, K. U. E., Fisher, L. W. SIBLING expression patterns in duct epithelia reflect the degree of metabolic activity. J. Histochem. Cytochem. 55: 403-409, 2007. [PubMed: 17210923] [Full Text: https://doi.org/10.1369/jhc.6A7075.2007]
Reinholt, F. P., Hultenby, K., Oldberg, A., Heinegard, D. Osteopontin--a possible anchor of osteoclasts to bone. Proc. Nat. Acad. Sci. 87: 4473-4475, 1990. [PubMed: 1693772] [Full Text: https://doi.org/10.1073/pnas.87.12.4473]
Renault, M.-A., Jalvy, S., Belloc, I., Pasquet, S., Sena, S., Olive, M., Desgranges, C., Gadeau, A.-P. AP-1 is involved in UTP-induced osteopontin expression in arterial smooth muscle cells. Circ. Res. 93: 674-681, 2003. [PubMed: 12970113] [Full Text: https://doi.org/10.1161/01.RES.0000094747.05021.62]
Rittling, S. R., Zetterberg, C., Yagiz, K., Skinner, S., Suzuki, N., Fujimura, A., Sasaki, H. Protective role of osteopontin in endodontic infection. Immunology 129: 105-114, 2009. [PubMed: 19824920] [Full Text: https://doi.org/10.1111/j.1365-2567.2009.03159.x]
Shinohara, M. L., Jansson, M., Hwang, E. S., Werneck, M. B. F., Glimcher, L. H., Cantor, H. T-bet-dependent expression of osteopontin contributes to T cell polarization. Proc. Nat. Acad. Sci. 102: 17101-17106, 2005. [PubMed: 16286640] [Full Text: https://doi.org/10.1073/pnas.0508666102]
Shinohara, M. L., Kim, H.-J., Kim, J.-H., Garcia, V. A., Cantor, H. Alternative translation of osteopontin generates intracellular and secreted isoforms that mediate distinct biological activities in dendritic cells. Proc. Nat. Acad. Sci. 105: 7235-7239, 2008. [PubMed: 18480255] [Full Text: https://doi.org/10.1073/pnas.0802301105]
Shinohara, M. L., Lu, L., Bu, J., Werneck, M. B. F., Kobayashi, K. S., Glimcher, L. H., Cantor, H. Osteopontin expression is essential for interferon-alpha production by plasmacytoid dendritic cells. Nature Immun. 7: 498-506, 2006. [PubMed: 16604075] [Full Text: https://doi.org/10.1038/ni1327]
Singh, K., Balligand, J.-L., Fischer, T. A., Smith, T. W., Kelly, R. A. Glucocorticoids increase osteopontin expression in cardiac myocytes and microvascular endothelial cells: role in regulation of inducible nitric oxide synthase. J. Biol. Chem. 270: 28471-28478, 1995. [PubMed: 7499354] [Full Text: https://doi.org/10.1074/jbc.270.47.28471]
Speer, M. Y., McKee, M. D., Guldberg, R. E., Liaw, L., Yang, H.-Y., Tung, E., Karsenty, G., Giachelli, C. M. 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. 196: 1047-1055, 2002. [PubMed: 12391016] [Full Text: https://doi.org/10.1084/jem.20020911]
Staal, A., van Wijnen, A. J., Birkenhager, J. C., Pols, H. A. P., Prahl, J., DeLuca, H., Gaub, M.-P., Lian, J. B., Stein, G. S., van Leeuwen, J. P. T. M., Stein, J. L. Distinct conformations of vitamin D receptor/retinoid X receptor-alpha heterodimers are specified by dinucleotide differences in the vitamin D-responsive elements of the osteocalcin and osteopontin genes. Molec. Endocr. 10: 1444-1456, 1996. [PubMed: 8923469] [Full Text: https://doi.org/10.1210/mend.10.11.8923469]
Steinman, L., Youssef, S., Van Venrooij, N., Chabas, D., Baranzini, S. E., Rittling, S., Denhardt, D., Sobel, R. A., Lock, C., Pedotti, R., Oksenberg, J. R. Response to comment on 'The influence of the proinflammatory cytokine, osteopontin, on autoimmune demyelinating disease.' Science 299: 1845 only, 2003. Note: Full text in Scienceonline.
Tagliabracci, V. S., Engel, J. L., Wen, J., Wiley, S. E., Worby, C. A., Kinch, L. N., Xiao, J., Grishin, N. V., Dixon, J. E. Secreted kinase phosphorylates extracellular proteins that regulate biomineralization. Science 336: 1150-1153, 2012. [PubMed: 22582013] [Full Text: https://doi.org/10.1126/science.1217817]
Weber, G. F., Ashkar, S., Glimcher, M. J., Cantor, H. Receptor-ligand interaction between CD44 and osteopontin (Eta-1). Science 271: 509-512, 1996. [PubMed: 8560266] [Full Text: https://doi.org/10.1126/science.271.5248.509]
Yamamoto, N., Sakai, F., Kon, S., Morimoto, J., Kimura, C., Yamazaki, H., Okazaki, I., Seki, N., Fujii, T., Uede, T. Essential role of the cryptic epitope SLAYGLR within osteopontin in a murine model of rheumatoid arthritis. J. Clin. Invest. 112: 181-188, 2003. [PubMed: 12865407] [Full Text: https://doi.org/10.1172/JCI17778]
Yoshitake, H., Rittling, S. R., Denhardt, D. T., Noda, M. Osteopontin-deficient mice are resistant to ovariectomy-induced bone resorption. Proc. Nat. Acad. Sci. 96: 8156-8160, 1999. Note: Erratum: Proc. Nat. Acad. Sci. 96: 10944 only, 1999. [PubMed: 10393964] [Full Text: https://doi.org/10.1073/pnas.96.14.8156]
Young, M. F., Kerr, J. M., Termine, J. D., Wewer, U. M., Wang, M. G., McBride, O. W., Fisher, L. W. cDNA cloning, mRNA distribution and heterogeneity, chromosomal location and RFLP analysis of human osteopontin. Genomics 7: 491-502, 1990. [PubMed: 1974876] [Full Text: https://doi.org/10.1016/0888-7543(90)90191-v]