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Proteoglycans and Osteolysis

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Proteoglycans

Part of the book series: Methods in Molecular Biology ((MIMB,volume 836))

Abstract

Osteolysis is a complex mechanism resulting from an exacerbated activity of osteoclasts associated or not with a dysregulation of osteoblast metabolism leading to bone loss. This bone defect is not compensated by bone apposition or by apposition of bone matrix with poor mechanical quality. Osteolytic process is regulated by mechanical constraints, by polypeptides including cytokines and hormones, and by extracellular matrix components such as proteoglycans (PGs) and glycosaminoglycans (GAGs). Several studies revealed that GAGs may influence osteoclastogenesis, but data are very controversial: some studies showed a repressive effect of GAGs on osteoclastic differentiation, whereas others described a stimulatory effect. The controversy also affects osteoblasts which appear sometimes inhibited by polysaccharides and sometimes stimulated by these compounds. Furthermore, long-term treatment with heparin leads to the development of osteoporosis fueling the controversy. After a brief description of the principal osteoclastogenesis assays, the present chapter summarizes the main data published on the effect of PGs/GAGs on bone cells and their functional incidence on osteolysis.

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References

  1. Bruzzaniti, A. and Baron, R. (2006) Molecular regulation of osteoclast activity. Rev Endocr Metab Disord. 7, 123–139.

    Article  PubMed  CAS  Google Scholar 

  2. Theoleyre, S., Wittrant, Y., Kwan Tat, S., Fortun, Y., Rédini, F., and Heymann, D. (2004) The molecular triad OPG/RANK/RANKL: involvement in the orchestration of pathophysiological bone remodeling. Cytokine Growth Factor Rev. 15, 457–475.

    Article  PubMed  CAS  Google Scholar 

  3. Heymann, D., Guicheux, J., Gouin, F., Passuti, N., and Daculsi, G. (1998) Cytokines, growth factors and osteoclasts. Cytokine 10, 155–168.

    Article  PubMed  CAS  Google Scholar 

  4. Baud’huin, M., Lamoureux, F., Duplomb, L., Rédini, F., and Heymann, D. (2007) RANKL, RANK, osteoprotegerin: key partners of osteoimmunology and vascular diseases. Cell Mol Life Sci 64, 2334–2350.

    Article  PubMed  Google Scholar 

  5. Rousselle, A.-V. and Heymann, D. (2002) Osteoclastic acidification pathways during bone resorption. Bone 30, 533–540.

    Article  PubMed  CAS  Google Scholar 

  6. Georges, S., Ruiz Velasco, C., Trichet, V., Fortun, Y., Heymann, D., and Padrines, M. (2009) Proteases and bone remodelling. Cytokine Growth Factor Rev 20, 29–41.

    Article  PubMed  CAS  Google Scholar 

  7. Marie, P. J. and Fromigué, O. (2006). Osteogenic differentiation of human marrow-derived mesenchymal stem cells. Regen Med 1, 539–548.

    Article  PubMed  CAS  Google Scholar 

  8. Damiens, C., Fortun, Y., Charrier, C., Heymann, D., and Padrines, M. (2000) Modulation by soluble factors of gelatinase activities released by osteoblastic cells. Cytokine 12, 1727–1731.

    Article  PubMed  CAS  Google Scholar 

  9. Lamoureux, F., Baud’huin, M., Duplomb, L., Heymann, D., and Rédini, F. (2007) Proteoglycans: key partners in bone cell biology. Bioessays 29, 758–771.

    Article  PubMed  CAS  Google Scholar 

  10. Boyle, W. J., Simonet, W. S., and Lacey, D. L. (2003) Osteoclast differentiation and activation. Nature 423, 337–342.

    Article  PubMed  CAS  Google Scholar 

  11. Wittrant, Y., Theoleyre, S., Couillaud, S., Dunstan, C., Heymann, D., and Rédini, F. (2004) Relevance of an in vitro osteoclastogenesis system to study receptor activator of NF-kB ligand and osteoprotegerin biological activities. Exp Cell Res. 293, 292–301.

    Article  PubMed  CAS  Google Scholar 

  12. Simonet, W. S., Lacey, D. L., Dunstan, C. R., Kelley, M., Chang, M. S., Luthy, R., et al (1997). Osteoprotegerin: a novel secreted protein involved in the regulation of bone density. Cell 89, 309–319.

    Article  PubMed  CAS  Google Scholar 

  13. Yasuda, H., Shima, N., Nakagawa, N., Mochizuki, S. I., Yano, K., Fujise, N., et al. (2004) Identity of osteoclastogenesis inhibitory factor (OCIF) and osteoprotegerin (OPG): a mechanism by which OPG/OCIF inhibits osteoclastogenesis in vitro. Endocrinology 139, 1329–1337.

    Article  Google Scholar 

  14. Corsi, A., Xu, T., Chen, X. D., Boyde, A., Liang, J., Mankani, M., et al (2002) Phenotypic effects of biglycan deficiency are linked to collagen fibril abnormalities, are synergized by decorin deficiency, and mimic Ehlers-Danlos-like changes in bone and other connective tissues. J Bone Miner Res. 17, 1180–1189.

    Article  PubMed  CAS  Google Scholar 

  15. Duplomb, L., Dagouassat, M., Jourdon, P., and Heymann, D. (2007) Concise review: embryonic stem cells: a new tool to study osteoblast and osteoclast differentiation. Stem Cells 25, 544–552.

    Article  PubMed  CAS  Google Scholar 

  16. Raschke, W. C., Baird, S., Ralph, P., and Nakoinz, I. (1978) Functional macrophage cell lines transformed by Abelson leukemia virus. Cell 15, 261–267.

    Article  PubMed  CAS  Google Scholar 

  17. Theoleyre, S., Wittrant, Y., Couillaud, S., Vusio, P., Berreur, M., Dunstan, C., et al (2004) Cellular activity and signaling induced by osteoprotegerin in osteoclasts: involvement of receptor activator of nuclear factor kappaB ligand and MAPK. Biochim Biophys Acta 1644, 1–7.

    Article  PubMed  CAS  Google Scholar 

  18. Blin-Wakkach, C., Breuil, V., Quincey, D., Bagnis, C., and Carle, G. F. (2006) Establishment and characterization of new osteoclast progenitor cell lines derived from osteopetrotic and wild type mice. Bone 39, 53–60.

    Article  PubMed  CAS  Google Scholar 

  19. Lézot, F, Thomas, B. L., Blin-Wakkach, C., Castaneda, B., Bolanos, A., Hotton, D., et al. (2010) Dlx homeobox gene family expression in osteoclasts. J Cell Physiol. 223, 779–787.

    PubMed  Google Scholar 

  20. Baud’huin, M., Duplomb, L., Téletchéa, S., Charrier, C., Maillasson, M., Fouassier, M., and Heymann, D. (2009) Factor VIII-von Willebrand factor complex inhibits osteoclastogenesis and controls cell survival. J Biol Chem. 284, 31704–31713.

    Article  PubMed  Google Scholar 

  21. Duplomb, L., Baud’huin, M., Charrier, C., Berreur, M., Trichet, V., Blanchard, F., and Heymann, D. (2008) Interleukin-6 inhibits receptor activator of nuclear factor kappaB ligand-induced osteoclastogenesis by diverting cells into the macrophage lineage: key role of Serine727 phosphorylation of signal transducer and activator of transcription 3. Endocrinology 149, 3688–3697.

    Article  PubMed  CAS  Google Scholar 

  22. Knowles, H. J. and Athanasou, N. A. (2009) Canonical and non-canonical pathways of osteoclast formation. Histol Histopathol 24, 337–346.

    PubMed  CAS  Google Scholar 

  23. Kong, Y. Y., Yoshida, H., Sarosi, I., Tan, H. L., Timms, E., Capparelli, C., et al. (1999) OPGL is a key regulator of osteoclastogenesis, lymphocyte development and lymph-node organogenesis. Nature 397, 315–323.

    Article  PubMed  CAS  Google Scholar 

  24. Baud’Huin, M., Renault, R., Charrier, C., Riet, A., Moreau, A, Brion R, et al. (2010) Interleukin-34 is expressed by giant cell tumours of bone and plays a key role in RANKL-induced osteoclastogenesis. J Pathol. 221, 77–86.

    Article  PubMed  Google Scholar 

  25. Chu, K., Snyder, R., Econs, M. J., and Facp, M. D. (2006) Disease status in autosomal dominant osteopetrosis type 2 is determined by osteoclastic properties. J Bone Miner Res. 21, 1089–1097.

    Article  PubMed  CAS  Google Scholar 

  26. Fuller, K., Kirstein, B., and Chambers, T. J. (2006) Murine osteoclast formation and function: differential regulation by humoral agents. Endocrinology 147, 1979–1985.

    Article  PubMed  CAS  Google Scholar 

  27. Baud’huin, M., Ruiz-Velasco, C., Jego, G., Charrier, C., Gasiunas, N., Gallagher J et al (2011) Glycosaminoglycans inhibit the adherence and the spreading of osteoclasts and their precursors: Role in osteoclastogenesis and bone resorption. Eur J Cell Biol. 60, 49–57.

    Article  Google Scholar 

  28. Gouin, F., Couillaud, S., Cottrel, M., Godard, A., Passuti, N., and Heymann, D. (1999) Presence of leukaemia inhibitory factor (LIF) and LIF-receptor chain (gp190) in osteoclast-like cells cultured from human giant cell tumour of bone. Ultrastructural distribution. Cytokine 11, 282–289.

    Article  PubMed  CAS  Google Scholar 

  29. Guicheux, J., Heymann, D., Rousselle, A.-V., Gouin, F., Pilet, P., Yamada, S., et al (1998) Growth hormone stimulatory effects on osteoclastic resorption are partly mediated by insulin-like growth factor I: an in vitro study. Bone 22, 25–31.

    Article  PubMed  CAS  Google Scholar 

  30. Kram, V., Zcharia, E., Yacoby-Zeevi, O., Metzger, S., Chajek-Shaul, T., Gabet, Y., et al (2006) Heparanase is expressed in osteoblastic cells and stimulates bone formation and bone mass. J Cell Physiol. 207, 784–792.

    Article  PubMed  CAS  Google Scholar 

  31. Ariyoshi, W., Takahashi, T., Kanno, T., Ichimiya, H., Shinmyouzu, K., Takano, H., et al (2008) Heparin inhibits osteoclastic differentiation and function. J Cell Biochem. 103, 1707–1717.

    Article  PubMed  CAS  Google Scholar 

  32. Shinmyouzu, K., Takahashi, T., Ariyoshi, W., Ichimiya, H., Kanzaki, S., and Nishihara, T. (2007) Dermatan sulfate inhibits osteoclast formation by binding to receptor activator of NF-kappa B ligand. Biochem Biophys Res Commun. 354, 447–452.

    Article  PubMed  CAS  Google Scholar 

  33. Irie, A., Takami, M., Kubo, H., Sekino-Suzuki, N., Kasahara, K., and Sanai, Y. (2007) Heparin enhances osteoclastic bone resorption by inhibiting osteoprotegerin activity. Bone 41, 165–174.

    Article  PubMed  CAS  Google Scholar 

  34. Ling, L., Murali, S., Stein, G. S., van Wijnen, A. J., and Cool, S. M. (2010) Glycosaminoglycans modulate RANKL-induced osteoclastogenesis. J Cell Biochem. 109, 1222–1231.

    PubMed  CAS  Google Scholar 

  35. Théoleyre, S., Kwan Tat, S., Vusio, P., Blanchard, F., Gallagher, J., Ricard-Blum, S., et al (2006) Characterization of osteoprotegerin binding to glycosaminoglycans by surface plasmon resonance: role in the interactions with receptor activator of nuclear factor kappaB ligand (RANKL) and RANK. Biochem Biophys Res Commun. 347, 460–467.

    Article  PubMed  Google Scholar 

  36. Lamoureux, F., Picarda, G., Garrigue-Antar, L., Baud’huin, M., Trichet, V., Vidal, A., et al (2009) Glycosaminoglycans as potential regulators of osteoprotegerin therapeutic activity in osteosarcoma. Cancer Res. 69, 526–536.

    Article  PubMed  CAS  Google Scholar 

  37. Chang, E. J., Kim, H. J., Ha, J., Kim, H. J., Ryu, J., Park, K. H., et al. (2007) Hyaluronan inhibits osteoclast differentiation via Toll-like receptor 4. J Cell Sci. 120, 166–176.

    Article  PubMed  CAS  Google Scholar 

  38. Pivetta, E., Scapolan, M., Wassermann, B., Steffan, A., Colombatti, A., and Spessotto, P. (2011) Blood-derived human osteoclast resorption activity is impaired by hyaluronan-CD44 engagement via a p38-dependent mechanism. J Cell Physiol. 226, 769–779.

    Article  PubMed  CAS  Google Scholar 

  39. Spessotto, P., Rossi, F. M., Degan, M., Di Francia, R., Perris, R., Colombatti, A., and Gattei, V. (2002) Hyaluronan-CD44 interaction hampers migration of osteoclast-like cells by down-regulating MMP-9. J Cell Biol. 158, 1133–1144.

    Article  PubMed  CAS  Google Scholar 

  40. Yamaguchi, K., Kinosaki, M., Goto, M., Kobayashi, F., Tsuda, E., Morinaga, T., et al (1998) Characterization of structural domains of human osteoclastogenesis inhibitory factor. J Biol Chem. 273, 5117–5123.

    Article  PubMed  CAS  Google Scholar 

  41. Standal, T., Seidel, C., Hjertner, O., Plesner, T., Sanderson, R. D., Waage, A., et al (2002) Osteoprotegerin is bound, internalized, and degraded by multiple myeloma cells. Blood 100, 3002– 3007.

    Article  PubMed  CAS  Google Scholar 

  42. Mosheimer, B. A., Kaneider, N. C., Feistritzer, C., Djanani, A. M., Sturn, D. H., Patsch, J. R., et al (2005) Syndecan-1 is involved in osteoprotegerin-induced chemotaxis in human peripheral blood monocytes, J Clin Endocrinol Metab. 90, 2964–2971.

    Article  PubMed  CAS  Google Scholar 

  43. Cool, S. M. and Nurcombe, V. (2005) The osteoblast-heparan sulfate axis: control of the bone cell lineage. Int J Biochem Cell Biol. 37, 1739–1745.

    Article  PubMed  CAS  Google Scholar 

  44. Cao, J. J., Singleton, P. A., Majumdar, S., Boudignon, B., Burghardt, A., Kurimoto, P., et al. (2005) Hyaluronan increases RANKL expression in bone marrow stromal cells through CD44. J Bone Miner Res. 20, 30–40.

    Article  PubMed  CAS  Google Scholar 

  45. Robinson, C. J., Harmer, N. J., Goodger, S. J., Blundell, T. L., and Gallagher, J. T. (2005) Cooperative dimerization of fibroblast growth factor 1 (FGF1) upon a single heparin saccharide may drive the formation of 2:2:1 FGF1.FGFR2c.heparin ternary complexes. J Biol Chem. 280, 42274–42282.

    Article  PubMed  CAS  Google Scholar 

  46. Presta, M., Dell’Era, P., Mitola, S., Moroni, E., Ronca, R., and Rusnati, M. (2005) Fibroblast growth factor/fibroblast growth factor receptor system in angiogenesis. Cytokine Growth Factor Rev 16, 159–178.

    Article  PubMed  CAS  Google Scholar 

  47. Jiao, X., Billings, P. C., O’Connell, M. P., Kaplan, F. S., Shore, E. M., and Glaser, D. L. (2007) Heparan sulfate proteoglycans (HSPGs) modulate BMP2 osteogenic bioactivity in C2C12 cells. J Biol Chem. 282, 1080–1086.

    Article  PubMed  CAS  Google Scholar 

  48. Song, S. J., Cool, S. M., and Nurcombe, V. (2007) Regulated expression of syndecan-4 in rat calvaria osteoblasts induced by fibroblast growth factor-2. J Cell Biochem. 100, 402–411.

    Article  PubMed  CAS  Google Scholar 

  49. Haupt, L. M., Murali, S., Mun, F. K., Teplyuk, N., Mei, L. F., Stein, G. S., et al (2009) The heparan sulfate proteoglycan (HSPG) glypican-3 mediates commitment of MC3T3-E1 cells toward osteogenesis. J Cell Physiol. 220, 780–791.

    Article  PubMed  CAS  Google Scholar 

  50. Fox, S. W. and Lovibond, A. C. (2005) Current insights into the role of transforming growth factor-beta in bone resorption. Mol Cell Endocrinol. 243, 19–26.

    Article  PubMed  CAS  Google Scholar 

  51. Bi, Y., Stuelten, C. H., Kilts, T., Wadhwa, S., Iozzo, R. V., Robey, P. G., et al (2005) Extracellular matrix proteoglycans control the fate of bone marrow stromal cells. J Biol Chem. 280, 30481–30489.

    Article  PubMed  CAS  Google Scholar 

  52. Bi, Y., Nielsen, K. L., Kilts, T. M., Yoon, A., Karsdal, M. A., Wimer, H. F., et al (2006) Biglycan deficiency increases osteoclast differentiation and activity due to defective osteoblasts, Bone 38, 30481–30489.

    Article  Google Scholar 

  53. Miyazaki, T., Miyauchi, S., Tawada, A., Anada, T., Matsuzaka, S., and Suzuki, O. (2008) Oversulfated chondroitin sulfate-E binds to BMP-4 and enhances osteoblast differentiation. J Cell Physiol. 217, 769–777.

    Article  PubMed  CAS  Google Scholar 

  54. Kumarasuriyar, A., Lee, I., Nurcombe, V., and Cool, S. M. (2009) De-sulfation of MG-63 cell glycosaminoglycans delays in vitro osteogenesis, up-regulates cholesterol synthesis and disrupts cell cycle and the actin cytoskeleton. J Cell Physiol. 219, 572–583.

    Article  PubMed  CAS  Google Scholar 

  55. Muir, J. M., Andrew, M., Hirsh, J., Weitz, J. I., Young, E., Deschamps, P., and Shaughnessy, S. G. (1996) Histomorphometric analysis of the effects of standard heparin on trabecular bone in vivo. Blood 88, 1314–1320.

    PubMed  CAS  Google Scholar 

  56. Muir, J. M., Hirsh, J., Weitz, J. I., Andrew, M., Young, E., and Shaughnessy, S. G. (1997) A histomorphometric comparison of the effects of heparin and low-molecular-weight heparin on cancellous bone in rats. Blood 89, 3236–3242.

    PubMed  CAS  Google Scholar 

  57. Ruiz-Velasco, C., Baud’huin, M., Sinquin, C., Maillasson, M., Heymann, D., Colliec-Jouault, S., and Padrines, M. (2011) Effects of a sulphated ‘heparin-like’ exopolysaccharide produced by Altermonas infernus on bone biology. Glycobiology, in press.

    Google Scholar 

  58. Barbour, L. A., Kick, S. D., Steiner, J. F., LoVerde, M. E., Heddleston, L. N., Lear, J. L., et al. (1994) A prospective study of heparin-induced osteoporosis in pregnancy using bone densitometry. Am J Obstet Gynecol. 170, 862–869.

    PubMed  CAS  Google Scholar 

  59. Folwarczna, J., Sliwiński, L., Janiec, W., and Pikul, M. (2005) Effects of standard heparin and low-molecular-weight heparins on the formation of murine osteoclasts in vitro. Pharmacol Rep. 57, 635–645.

    PubMed  CAS  Google Scholar 

  60. Rajgopal, R., Bear, M., Butcher, M. K., and Shaughnessy, S. G. (2008) The effects of heparin and low molecular weight heparins on bone. Thromb Res. 122, 293–298.

    Article  PubMed  CAS  Google Scholar 

  61. Nakano, K., Okada, Y., Saito, K., and Tanaka, Y. (2004) Induction of RANKL expression and osteoclast maturation by the binding of fibroblast growth factor 2 to heparan sulfate proteoglycan on rheumatoid synovial fibroblasts. Arthritis Rheum. 50, 2450–2458.

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. INSERM, UMR 957, Nantes, France

    Marc Baud’Huin, Céline Charrier, Gwenola Bougras, Régis Brion & Frédéric Lezot

  2. Physiopathologie de la Résorption Osseuse et Thérapie des Tumeurs Osseuses Primitives, Université de Nantes, Nantes Atlantique Universités, Nantes, France

    Marc Baud’Huin, Céline Charrier, Gwenola Bougras, Régis Brion & Frédéric Lezot

  3. INSERM, U957, Nantes, France

    Marc Padrines & Dominique Heymann

  4. Laboratoire de Physiopathologie de la Résorption Osseuse et Thérapie des Tumeurs Osseuses Primitives, Université de Nantes, Nantes Atlantique Universités, Nantes, France

    Marc Padrines & Dominique Heymann

  5. Centre Hospitalier Universitaire de Nantes, Nantes, France

    Dominique Heymann

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  1. Marc Baud’Huin
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  2. Céline Charrier
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Correspondence to Dominique Heymann .

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  1. , Faculté de Médicine, INSERM U957 - EA 3822, rue Gaston Veil 1, Nantes, 44035, France

    Françoise Rédini

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Baud’Huin, M. et al. (2012). Proteoglycans and Osteolysis. In: Rédini, F. (eds) Proteoglycans. Methods in Molecular Biology, vol 836. Humana Press. https://doi.org/10.1007/978-1-61779-498-8_21

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  • DOI: https://doi.org/10.1007/978-1-61779-498-8_21

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