Skip to main content
NCBI home page
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1992 Jan 1;89(1):426–430. doi: 10.1073/pnas.89.1.426

Inhibition of calcium oxalate crystal growth in vitro by uropontin: another member of the aspartic acid-rich protein superfamily.

H Shiraga 1, W Min 1, W J VanDusen 1, M D Clayman 1, D Miner 1, C H Terrell 1, J R Sherbotie 1, J W Foreman 1, C Przysiecki 1, E G Neilson 1, et al.
PMCID: PMC48250  PMID: 1729712

Abstract

The majority of human urinary stones are primarily composed of calcium salts. Although normal urine is frequently supersaturated with respect to calcium oxalate, most humans do not form stones. Inhibitors are among the multiple factors that may influence the complex process of urinary stone formation. We have isolated an inhibitor of calcium oxalate crystal growth from human urine by monoclonal antibody immunoaffinity chromatography. The N-terminal amino acid sequence and acidic amino acid content of this aspartic acid-rich protein, uropontin, are similar to those of other pontin proteins from bone, plasma, breast milk, and cells. The inhibitory effect of uropontin on calcium oxalate crystal growth in vitro supports the concept that pontins may have a regulatory role. This function would be analogous to that of other members of the aspartic acid-rich protein superfamily, which stereospecifically regulate the mineralization fronts of calcium-containing crystals.

Full text

PDF
426

Images in this article

427Image
on p.427
428Image
on p.428

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Addadi L., Moradian J., Shay E., Maroudas N. G., Weiner S. A chemical model for the cooperation of sulfates and carboxylates in calcite crystal nucleation: Relevance to biomineralization. Proc Natl Acad Sci U S A. 1987 May;84(9):2732–2736. doi: 10.1073/pnas.84.9.2732. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Addadi L., Weiner S. Interactions between acidic proteins and crystals: stereochemical requirements in biomineralization. Proc Natl Acad Sci U S A. 1985 Jun;82(12):4110–4114. doi: 10.1073/pnas.82.12.4110. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Campbell A. A., Ebrahimpour A., Perez L., Smesko S. A., Nancollas G. H. The dual role of polyelectrolytes and proteins as mineralization promoters and inhibitors of calcium oxalate monohydrate. Calcif Tissue Int. 1989 Aug;45(2):122–128. doi: 10.1007/BF02561411. [DOI] [PubMed] [Google Scholar]
  4. Clayman M. D., Martinez-Hernandez A., Michaud L., Alper R., Mann R., Kefalides N. A., Neilson E. G. Isolation and characterization of the nephritogenic antigen producing anti-tubular basement membrane disease. J Exp Med. 1985 Feb 1;161(2):290–305. doi: 10.1084/jem.161.2.290. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Coe F., Parks J. H. Defenses of an unstable compromise: crystallization inhibitors and the kidney's role in mineral regulation. Kidney Int. 1990 Oct;38(4):625–631. doi: 10.1038/ki.1990.252. [DOI] [PubMed] [Google Scholar]
  6. Craig A. M., Nemir M., Mukherjee B. B., Chambers A. F., Denhardt D. T. Identification of the major phosphoprotein secreted by many rodent cell lines as 2ar/osteopontin: enhanced expression in H-ras-transformed 3T3 cells. Biochem Biophys Res Commun. 1988 Nov 30;157(1):166–173. doi: 10.1016/s0006-291x(88)80028-7. [DOI] [PubMed] [Google Scholar]
  7. Craig A. M., Smith J. H., Denhardt D. T. Osteopontin, a transformation-associated cell adhesion phosphoprotein, is induced by 12-O-tetradecanoylphorbol 13-acetate in mouse epidermis. J Biol Chem. 1989 Jun 5;264(16):9682–9689. [PubMed] [Google Scholar]
  8. Fisher L. W., Hawkins G. R., Tuross N., Termine J. D. Purification and partial characterization of small proteoglycans I and II, bone sialoproteins I and II, and osteonectin from the mineral compartment of developing human bone. J Biol Chem. 1987 Jul 15;262(20):9702–9708. [PubMed] [Google Scholar]
  9. Kiefer M. C., Bauer D. M., Barr P. J. The cDNA and derived amino acid sequence for human osteopontin. Nucleic Acids Res. 1989 Apr 25;17(8):3306–3306. doi: 10.1093/nar/17.8.3306. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Kubota T., Zhang Q., Wrana J. L., Ber R., Aubin J. E., Butler W. T., Sodek J. Multiple forms of SppI (secreted phosphoprotein, osteopontin) synthesized by normal and transformed rat bone cell populations: regulation by TGF-beta. Biochem Biophys Res Commun. 1989 Aug 15;162(3):1453–1459. doi: 10.1016/0006-291x(89)90837-1. [DOI] [PubMed] [Google Scholar]
  11. Laemmli U. K. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 1970 Aug 15;227(5259):680–685. doi: 10.1038/227680a0. [DOI] [PubMed] [Google Scholar]
  12. Lee S. L., Veis A., Glonek T. Dentin phosphoprotein: an extracellular calcium-binding protein. Biochemistry. 1977 Jun 28;16(13):2971–2979. doi: 10.1021/bi00632a026. [DOI] [PubMed] [Google Scholar]
  13. Lian J. B., Prien E. L., Jr, Glimcher M. J., Gallop P. M. The presence of protein-bound gamma-carboxyglutamic acid in calcium-containing renal calculi. J Clin Invest. 1977 Jun;59(6):1151–1157. doi: 10.1172/JCI108739. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Ligabue A., Fini M., Robertson W. G. Influence of urine on "in vitro" crystallization rate of calcium oxalate: determination of inhibitory activity by a [14C]oxalate technique. Clin Chim Acta. 1979 Oct 15;98(1-2):39–46. doi: 10.1016/0009-8981(79)90163-3. [DOI] [PubMed] [Google Scholar]
  15. Linde A., Lussi A., Crenshaw M. A. Mineral induction by immobilized polyanionic proteins. Calcif Tissue Int. 1989 Apr;44(4):286–295. doi: 10.1007/BF02553763. [DOI] [PubMed] [Google Scholar]
  16. Mark M. P., Butler W. T., Prince C. W., Finkelman R. D., Ruch J. V. Developmental expression of 44-kDa bone phosphoprotein (osteopontin) and bone gamma-carboxyglutamic acid (Gla)-containing protein (osteocalcin) in calcifying tissues of rat. Differentiation. 1988;37(2):123–136. doi: 10.1111/j.1432-0436.1988.tb00804.x. [DOI] [PubMed] [Google Scholar]
  17. Mark M. P., Prince C. W., Gay S., Austin R. L., Butler W. T. 44-kDal bone phosphoprotein (osteopontin) antigenicity at ectopic sites in newborn rats: kidney and nervous tissues. Cell Tissue Res. 1988 Jan;251(1):23–30. doi: 10.1007/BF00215443. [DOI] [PubMed] [Google Scholar]
  18. Meyer J. L., Smith L. H. Growth of calcium oxalate crystals. II. Inhibition by natural urinary crystal growth inhibitors. Invest Urol. 1975 Jul;13(1):36–39. [PubMed] [Google Scholar]
  19. Miyazaki Y., Setoguchi M., Yoshida S., Higuchi Y., Akizuki S., Yamamoto S. Nucleotide sequence of cDNA for mouse osteopontin-like protein. Nucleic Acids Res. 1989 Apr 25;17(8):3298–3298. doi: 10.1093/nar/17.8.3298. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Miyazaki Y., Setoguchi M., Yoshida S., Higuchi Y., Akizuki S., Yamamoto S. The mouse osteopontin gene. Expression in monocytic lineages and complete nucleotide sequence. J Biol Chem. 1990 Aug 25;265(24):14432–14438. [PubMed] [Google Scholar]
  21. Nagata T., Bellows C. G., Kasugai S., Butler W. T., Sodek J. Biosynthesis of bone proteins [SPP-1 (secreted phosphoprotein-1, osteopontin), BSP (bone sialoprotein) and SPARC (osteonectin)] in association with mineralized-tissue formation by fetal-rat calvarial cells in culture. Biochem J. 1991 Mar 1;274(Pt 2):513–520. doi: 10.1042/bj2740513. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Nakagawa Y., Abram V., Kézdy F. J., Kaiser E. T., Coe F. L. Purification and characterization of the principal inhibitor of calcium oxalate monohydrate crystal growth in human urine. J Biol Chem. 1983 Oct 25;258(20):12594–12600. [PubMed] [Google Scholar]
  23. Nakagawa Y., Ahmed M., Hall S. L., Deganello S., Coe F. L. Isolation from human calcium oxalate renal stones of nephrocalcin, a glycoprotein inhibitor of calcium oxalate crystal growth. Evidence that nephrocalcin from patients with calcium oxalate nephrolithiasis is deficient in gamma-carboxyglutamic acid. J Clin Invest. 1987 Jun;79(6):1782–1787. doi: 10.1172/JCI113019. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Noda M., Rodan G. A. Transcriptional regulation of osteopontin production in rat osteoblast-like cells by parathyroid hormone. J Cell Biol. 1989 Feb;108(2):713–718. doi: 10.1083/jcb.108.2.713. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Noda M., Vogel R. L., Craig A. M., Prahl J., DeLuca H. F., Denhardt D. T. Identification of a DNA sequence responsible for binding of the 1,25-dihydroxyvitamin D3 receptor and 1,25-dihydroxyvitamin D3 enhancement of mouse secreted phosphoprotein 1 (SPP-1 or osteopontin) gene expression. Proc Natl Acad Sci U S A. 1990 Dec;87(24):9995–9999. doi: 10.1073/pnas.87.24.9995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Nomura S., Wills A. J., Edwards D. R., Heath J. K., Hogan B. L. Developmental expression of 2ar (osteopontin) and SPARC (osteonectin) RNA as revealed by in situ hybridization. J Cell Biol. 1988 Feb;106(2):441–450. doi: 10.1083/jcb.106.2.441. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Oldberg A., Franzén A., Heinegård D. Cloning and sequence analysis of rat bone sialoprotein (osteopontin) cDNA reveals an Arg-Gly-Asp cell-binding sequence. Proc Natl Acad Sci U S A. 1986 Dec;83(23):8819–8823. doi: 10.1073/pnas.83.23.8819. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Patarca R., Freeman G. J., Singh R. P., Wei F. Y., Durfee T., Blattner F., Regnier D. C., Kozak C. A., Mock B. A., Morse H. C., 3rd Structural and functional studies of the early T lymphocyte activation 1 (Eta-1) gene. Definition of a novel T cell-dependent response associated with genetic resistance to bacterial infection. J Exp Med. 1989 Jul 1;170(1):145–161. doi: 10.1084/jem.170.1.145. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Prince C. W., Butler W. T. 1,25-Dihydroxyvitamin D3 regulates the biosynthesis of osteopontin, a bone-derived cell attachment protein, in clonal osteoblast-like osteosarcoma cells. Coll Relat Res. 1987 Sep;7(4):305–313. doi: 10.1016/s0174-173x(87)80036-5. [DOI] [PubMed] [Google Scholar]
  30. Prince C. W., Oosawa T., Butler W. T., Tomana M., Bhown A. S., Bhown M., Schrohenloher R. E. Isolation, characterization, and biosynthesis of a phosphorylated glycoprotein from rat bone. J Biol Chem. 1987 Feb 25;262(6):2900–2907. [PubMed] [Google Scholar]
  31. Przysiecki C. T., Staggers J. E., Ramjit H. G., Musson D. G., Stern A. M., Bennett C. D., Friedman P. A. Occurrence of beta-hydroxylated asparagine residues in non-vitamin K-dependent proteins containing epidermal growth factor-like domains. Proc Natl Acad Sci U S A. 1987 Nov;84(22):7856–7860. doi: 10.1073/pnas.84.22.7856. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Reinholt F. P., Hultenby K., Oldberg A., Heinegård D. Osteopontin--a possible anchor of osteoclasts to bone. Proc Natl Acad Sci U S A. 1990 Jun;87(12):4473–4475. doi: 10.1073/pnas.87.12.4473. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Romberg R. W., Werness P. G., Riggs B. L., Mann K. G. Inhibition of hydroxyapatite crystal growth by bone-specific and other calcium-binding proteins. Biochemistry. 1986 Mar 11;25(5):1176–1180. doi: 10.1021/bi00353a035. [DOI] [PubMed] [Google Scholar]
  34. Senger D. R., Perruzzi C. A., Papadopoulos A., Tenen D. G. Purification of a human milk protein closely similar to tumor-secreted phosphoproteins and osteopontin. Biochim Biophys Acta. 1989 Jun 13;996(1-2):43–48. doi: 10.1016/0167-4838(89)90092-7. [DOI] [PubMed] [Google Scholar]
  35. Singh K., DeVouge M. W., Mukherjee B. B. Physiological properties and differential glycosylation of phosphorylated and nonphosphorylated forms of osteopontin secreted by normal rat kidney cells. J Biol Chem. 1990 Oct 25;265(30):18696–18701. [PubMed] [Google Scholar]
  36. Spector A. R., Gray A., Prien E. L., Jr Kidney stone matrix. Differences in acidic protein composition. Invest Urol. 1976 May;13(6):387–389. [PubMed] [Google Scholar]
  37. Stein G. S., Lian J. B., Owen T. A. Relationship of cell growth to the regulation of tissue-specific gene expression during osteoblast differentiation. FASEB J. 1990 Oct;4(13):3111–3123. doi: 10.1096/fasebj.4.13.2210157. [DOI] [PubMed] [Google Scholar]
  38. Swanson G. J., Nomura S., Hogan B. L. Distribution of expression of 2AR (osteopontin) in the embryonic mouse inner ear revealed by in situ hybridisation. Hear Res. 1989 Sep;41(2-3):169–177. doi: 10.1016/0378-5955(89)90008-7. [DOI] [PubMed] [Google Scholar]
  39. TAMM I., HORSFALL F. L., Jr Characterization and separation of an inhibitor of viral hemagglutination present in urine. Proc Soc Exp Biol Med. 1950 May;74(1):106–108. [PubMed] [Google Scholar]
  40. Termine J. D., Eanes E. D., Conn K. M. Phosphoprotein modulation of apatite crystallization. Calcif Tissue Int. 1980;31(3):247–251. doi: 10.1007/BF02407188. [DOI] [PubMed] [Google Scholar]
  41. Towbin H., Staehelin T., Gordon J. Electrophoretic transfer of proteins from polyacrylamide gels to nitrocellulose sheets: procedure and some applications. Proc Natl Acad Sci U S A. 1979 Sep;76(9):4350–4354. doi: 10.1073/pnas.76.9.4350. [DOI] [PMC free article] [PubMed] [Google Scholar]
  42. Weiner S., Hood L. Soluble protein of the organic matrix of mollusk shells: a potential template for shell formation. Science. 1975 Dec 5;190(4218):987–989. doi: 10.1126/science.1188379. [DOI] [PubMed] [Google Scholar]
  43. Wheeler A. P., George J. W., Evans C. A. Control of calcium carbonate nucleation and crystal growth by soluble matrx of oyster shell. Science. 1981 Jun 19;212(4501):1397–1398. doi: 10.1126/science.212.4501.1397. [DOI] [PubMed] [Google Scholar]
  44. Worcester E. M., Nakagawa Y., Wabner C. L., Kumar S., Coe F. L. Crystal adsorption and growth slowing by nephrocalcin, albumin, and Tamm-Horsfall protein. Am J Physiol. 1988 Dec;255(6 Pt 2):F1197–F1205. doi: 10.1152/ajprenal.1988.255.6.F1197. [DOI] [PubMed] [Google Scholar]
  45. Wrana J. L., Zhang Q., Sodek J. Full length cDNA sequence of porcine secreted phosphoprotein-I (SPP-I, osteopontin). Nucleic Acids Res. 1989 Dec 11;17(23):10119–10119. doi: 10.1093/nar/17.23.10119. [DOI] [PMC free article] [PubMed] [Google Scholar]
  46. Yoon K., Buenaga R., Rodan G. A. Tissue specificity and developmental expression of rat osteopontin. Biochem Biophys Res Commun. 1987 Nov 13;148(3):1129–1136. doi: 10.1016/s0006-291x(87)80250-4. [DOI] [PubMed] [Google Scholar]
  47. Yoshioka T., Shiraga H., Yoshida Y., Fogo A., Glick A. D., Deen W. M., Hoyer J. R., Ichikawa I. "Intact nephrons" as the primary origin of proteinuria in chronic renal disease. Study in the rat model of subtotal nephrectomy. J Clin Invest. 1988 Nov;82(5):1614–1623. doi: 10.1172/JCI113773. [DOI] [PMC free article] [PubMed] [Google Scholar]
  48. 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 (OPN). Genomics. 1990 Aug;7(4):491–502. doi: 10.1016/0888-7543(90)90191-v. [DOI] [PubMed] [Google Scholar]
  49. van de Loo P. G., Soute B. A., van Haarlem L. J., Vermeer C. The effect of Gla-containing proteins on the precipitation of insoluble salts. Biochem Biophys Res Commun. 1987 Jan 15;142(1):113–119. doi: 10.1016/0006-291x(87)90458-x. [DOI] [PubMed] [Google Scholar]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES