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. 1994 Dec 2;127(6):1767–1775. doi: 10.1083/jcb.127.6.1767

A potential role for tetranectin in mineralization during osteogenesis

PMCID: PMC2120295  PMID: 7798325

Abstract

Tetranectin is a protein shared by the blood and the extracellular matrix. Tetranectin is composed of four identical, noncovalently bound polypeptides each with a molecular mass of approximately 21 kD. There is some evidence that tetranectin may be involved in fibrinolysis and proteolysis during tissue remodeling, but its precise biological function is not known. Tetranectin is enriched in the cartilage of the shark, but the gene expression pattern in the mammalian skeletal system has not been determined. In the present study we have examined the expression pattern and putative function of tetranectin during osteogenesis. In the newborn mouse, strong tetranectin immunoreactivity was found in the newly formed woven bone around the cartilage anlage in the future bone marrow and along the periosteum forming the cortex. No tetranectin immunoreactivity was found in the proliferating and hypertrophic cartilage or in the surrounding skeletal muscle. Using an in vitro mineralizing system, we examined osteoblastic cells at different times during their growth and differentiation. Tetranectin mRNA appeared in the cultured osteoblastic cells in parallel with mineralization, in a pattern similar to that of bone sialoprotein, which is regarded as one of the late bone differentiation markers. To explore the putative biological role of tetranectin in osteogenesis we established stably transfected cell lines (PC12-tet) overexpressing recombinant tetranectin as evidenced by Northern and Western blot analysis and immunoprecipitation. Both control PC12 cells and PC12-tet cells injected into nude mice produced tumors containing bone material, as evidenced by von Kossa staining for calcium and immunostaining with bone sialoprotein and alkaline phosphatase antiserum. Nude mice tumors established from PC12-tet cells contained approximately fivefold more bone material than those produced by the untransfected PC12 cell line or by the PC12 cells transfected with the expression vector with no insert (Mann Whitney rank sum test, p < 0.01), supporting the notion that tetranectin may play an important direct and/or indirect role during osteogenesis. In conclusion, we have established a potential role for tetranectin as a bone matrix protein expressed in time and space coincident with mineralization in vivo and in vitro.

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Selected References

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  1. ANDERSON H. C., MERKER P. C., FOCH J. FORMATION OF TUMORS CONTAINING BONE AFTER INTRAMUSCULAR INJECTION OF TRANSFORMED HUMAN AMNION CELLS (FL) INTO CORTISONE-TREATED MICE. Am J Pathol. 1964 Mar;44:507–519. [PMC free article] [PubMed] [Google Scholar]
  2. Barone L. M., Owen T. A., Tassinari M. S., Bortell R., Stein G. S., Lian J. B. Developmental expression and hormonal regulation of the rat matrix Gla protein (MGP) gene in chondrogenesis and osteogenesis. J Cell Biochem. 1991 Aug;46(4):351–365. doi: 10.1002/jcb.240460410. [DOI] [PubMed] [Google Scholar]
  3. Berglund L., Petersen T. E. The gene structure of tetranectin, a plasminogen binding protein. FEBS Lett. 1992 Aug 31;309(1):15–19. doi: 10.1016/0014-5793(92)80729-z. [DOI] [PubMed] [Google Scholar]
  4. Bianco P., Fisher L. W., Young M. F., Termine J. D., Robey P. G. Expression and localization of the two small proteoglycans biglycan and decorin in developing human skeletal and non-skeletal tissues. J Histochem Cytochem. 1990 Nov;38(11):1549–1563. doi: 10.1177/38.11.2212616. [DOI] [PubMed] [Google Scholar]
  5. Bianco P., Fisher L. W., Young M. F., Termine J. D., Robey P. G. Expression of bone sialoprotein (BSP) in developing human tissues. Calcif Tissue Int. 1991 Dec;49(6):421–426. doi: 10.1007/BF02555854. [DOI] [PubMed] [Google Scholar]
  6. Border W. A., Noble N. A., Yamamoto T., Harper J. R., Yamaguchi Y. u., Pierschbacher M. D., Ruoslahti E. Natural inhibitor of transforming growth factor-beta protects against scarring in experimental kidney disease. Nature. 1992 Nov 26;360(6402):361–364. doi: 10.1038/360361a0. [DOI] [PubMed] [Google Scholar]
  7. Borregaard N., Christensen L., Bejerrum O. W., Birgens H. S., Clemmensen I. Identification of a highly mobilizable subset of human neutrophil intracellular vesicles that contains tetranectin and latent alkaline phosphatase. J Clin Invest. 1990 Feb;85(2):408–416. doi: 10.1172/JCI114453. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Boyan B. D., Swain L. D., Schwartz Z., Ramirez V., Carnes D. L., Jr Epithelial cell lines that induce bone formation in vivo produce alkaline phosphatase-enriched matrix vesicles in culture. Clin Orthop Relat Res. 1992 Apr;(277):266–276. [PubMed] [Google Scholar]
  9. Chiquet-Ehrismann R., Mackie E. J., Pearson C. A., Sakakura T. Tenascin: an extracellular matrix protein involved in tissue interactions during fetal development and oncogenesis. Cell. 1986 Oct 10;47(1):131–139. doi: 10.1016/0092-8674(86)90374-0. [DOI] [PubMed] [Google Scholar]
  10. Chomczynski P., Sacchi N. Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal Biochem. 1987 Apr;162(1):156–159. doi: 10.1006/abio.1987.9999. [DOI] [PubMed] [Google Scholar]
  11. Christensen L., Clemmensen I. Differences in tetranectin immunoreactivity between benign and malignant breast tissue. Histochemistry. 1991;95(5):427–433. doi: 10.1007/BF00315737. [DOI] [PubMed] [Google Scholar]
  12. Christensen L., Clemmensen I. Tetranectin immunoreactivity in normal human tissues. An immunohistochemical study of exocrine epithelia and mesenchyme. Histochemistry. 1989;92(1):29–35. doi: 10.1007/BF00495012. [DOI] [PubMed] [Google Scholar]
  13. Christensen L., Johansen N., Jensen B. A., Clemmensen I. Immunohistochemical localization of a novel, human plasma protein, tetranectin, in human endocrine tissues. Histochemistry. 1987;87(3):195–199. doi: 10.1007/BF00492409. [DOI] [PubMed] [Google Scholar]
  14. Clemmensen I. Interaction of tetranectin with sulphated polysaccharides and trypan blue. Scand J Clin Lab Invest. 1989 Dec;49(8):719–725. doi: 10.3109/00365518909091550. [DOI] [PubMed] [Google Scholar]
  15. Clemmensen I., Lund L. R., Christensen L., Andreasen P. A. A tetranectin-related protein is produced and deposited in extracellular matrix by human embryonal fibroblasts. Eur J Biochem. 1991 Feb 14;195(3):735–741. doi: 10.1111/j.1432-1033.1991.tb15761.x. [DOI] [PubMed] [Google Scholar]
  16. Clemmensen I., Petersen L. C., Kluft C. Purification and characterization of a novel, oligomeric, plasminogen kringle 4 binding protein from human plasma: tetranectin. Eur J Biochem. 1986 Apr 15;156(2):327–333. doi: 10.1111/j.1432-1033.1986.tb09586.x. [DOI] [PubMed] [Google Scholar]
  17. Fuhlendorff J., Clemmensen I., Magnusson S. Primary structure of tetranectin, a plasminogen kringle 4 binding plasma protein: homology with asialoglycoprotein receptors and cartilage proteoglycan core protein. Biochemistry. 1987 Oct 20;26(21):6757–6764. doi: 10.1021/bi00395a027. [DOI] [PubMed] [Google Scholar]
  18. Gough N. M. Rapid and quantitative preparation of cytoplasmic RNA from small numbers of cells. Anal Biochem. 1988 Aug 15;173(1):93–95. doi: 10.1016/0003-2697(88)90164-9. [DOI] [PubMed] [Google Scholar]
  19. Greene L. A., Tischler A. S. Establishment of a noradrenergic clonal line of rat adrenal pheochromocytoma cells which respond to nerve growth factor. Proc Natl Acad Sci U S A. 1976 Jul;73(7):2424–2428. doi: 10.1073/pnas.73.7.2424. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Hauschka P. V., Lian J. B., Cole D. E., Gundberg C. M. Osteocalcin and matrix Gla protein: vitamin K-dependent proteins in bone. Physiol Rev. 1989 Jul;69(3):990–1047. doi: 10.1152/physrev.1989.69.3.990. [DOI] [PubMed] [Google Scholar]
  21. Hoylaerts M. F., Millán J. L. Site-directed mutagenesis and epitope-mapped monoclonal antibodies define a catalytically important conformational difference between human placental and germ cell alkaline phosphatase. Eur J Biochem. 1991 Dec 5;202(2):605–616. doi: 10.1111/j.1432-1033.1991.tb16414.x. [DOI] [PubMed] [Google Scholar]
  22. Ibaraki K., Termine J. D., Whitson S. W., Young M. F. Bone matrix mRNA expression in differentiating fetal bovine osteoblasts. J Bone Miner Res. 1992 Jul;7(7):743–754. doi: 10.1002/jbmr.5650070704. [DOI] [PubMed] [Google Scholar]
  23. Jensen B. A., Clemmensen I. Plasma tetranectin is reduced in cancer and related to metastasia. Cancer. 1988 Sep 1;62(5):869–872. doi: 10.1002/1097-0142(19880901)62:5<869::aid-cncr2820620503>3.0.co;2-6. [DOI] [PubMed] [Google Scholar]
  24. Kluft C., Jie A. F., Los P., de Wit E., Havekes L. Functional analogy between lipoprotein(a) and plasminogen in the binding to the kringle 4 binding protein, tetranectin. Biochem Biophys Res Commun. 1989 Jun 15;161(2):427–433. doi: 10.1016/0006-291x(89)92616-8. [DOI] [PubMed] [Google Scholar]
  25. Kluft C., Los P., Clemmensen I. Calcium-dependent binding of tetranectin to fibrin. Thromb Res. 1989 Jul 15;55(2):233–238. doi: 10.1016/0049-3848(89)90440-4. [DOI] [PubMed] [Google Scholar]
  26. 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]
  27. 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]
  28. Midura R. J., McQuillan D. J., Benham K. J., Fisher L. W., Hascall V. C. A rat osteogenic cell line (UMR 106-01) synthesizes a highly sulfated form of bone sialoprotein. J Biol Chem. 1990 Mar 25;265(9):5285–5291. [PubMed] [Google Scholar]
  29. Neame P. J., Young C. N., Treep J. T. Primary structure of a protein isolated from reef shark (Carcharhinus springeri) cartilage that is similar to the mammalian C-type lectin homolog, tetranectin. Protein Sci. 1992 Jan;1(1):161–168. doi: 10.1002/pro.5560010116. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Owen T. A., Aronow M. S., Barone L. M., Bettencourt B., Stein G. S., Lian J. B. Pleiotropic effects of vitamin D on osteoblast gene expression are related to the proliferative and differentiated state of the bone cell phenotype: dependency upon basal levels of gene expression, duration of exposure, and bone matrix competency in normal rat osteoblast cultures. Endocrinology. 1991 Mar;128(3):1496–1504. doi: 10.1210/endo-128-3-1496. [DOI] [PubMed] [Google Scholar]
  31. Raines E. W., Lane T. F., Iruela-Arispe M. L., Ross R., Sage E. H. The extracellular glycoprotein SPARC interacts with platelet-derived growth factor (PDGF)-AB and -BB and inhibits the binding of PDGF to its receptors. Proc Natl Acad Sci U S A. 1992 Feb 15;89(4):1281–1285. doi: 10.1073/pnas.89.4.1281. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Reing J., Durkin M. E., Chung A. E. Laminin B1 expression is required for laminin deposition into the extracellular matrix of PC12 cells. J Biol Chem. 1992 Nov 15;267(32):23143–23150. [PubMed] [Google Scholar]
  33. Sage H., Vernon R. B., Decker J., Funk S., Iruela-Arispe M. L. Distribution of the calcium-binding protein SPARC in tissues of embryonic and adult mice. J Histochem Cytochem. 1989 Jun;37(6):819–829. doi: 10.1177/37.6.2723400. [DOI] [PubMed] [Google Scholar]
  34. Urist M. R., DeLange R. J., Finerman G. A. Bone cell differentiation and growth factors. Science. 1983 May 13;220(4598):680–686. doi: 10.1126/science.6403986. [DOI] [PubMed] [Google Scholar]
  35. Weinreb M., Shinar D., Rodan G. A. Different pattern of alkaline phosphatase, osteopontin, and osteocalcin expression in developing rat bone visualized by in situ hybridization. J Bone Miner Res. 1990 Aug;5(8):831–842. doi: 10.1002/jbmr.5650050806. [DOI] [PubMed] [Google Scholar]
  36. Wewer U. M., Albrechtsen R. Tetranectin, a plasminogen kringle 4-binding protein. Cloning and gene expression pattern in human colon cancer. Lab Invest. 1992 Aug;67(2):253–262. [PubMed] [Google Scholar]
  37. Whitson S. W., Whitson M. A., Bowers D. E., Jr, Falk M. C. Factors influencing synthesis and mineralization of bone matrix from fetal bovine bone cells grown in vitro. J Bone Miner Res. 1992 Jul;7(7):727–741. doi: 10.1002/jbmr.5650070703. [DOI] [PubMed] [Google Scholar]
  38. Wlodarski K. The inductive properties of epithelial established cell lines. Exp Cell Res. 1969 Oct;57(2):446–448. doi: 10.1016/0014-4827(69)90172-4. [DOI] [PubMed] [Google Scholar]

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