Skip to main content
SpringerLink
Log in

The effect of the alendronate on OPG/RANKL system in differentiated primary human osteoblasts

  • Original Article
  • Published:
Endocrine Aims and scope Submit manuscript

Abstract

Alendronate is a well-established treatment for osteoporosis and suppresses bone resorption by a direct effect on osteoclasts and their precursors. The effect of alendronate on osteoclasts is produced, at least in part, by the receptor activator of nuclear factor kappaB ligand (RANKL) and the osteoprotegerin (OPG) synthesized by the osteoblasts. This study analyzes the effect of alendronate in cell viability, alkaline phosphatase (ALP) activity and RANKL and OPG expression in primary human osteoblasts (hOB). Alendronate at concentrations lower than 10−5 M did not have a toxic effect on hOB in vitro and did not modify the ALP activity at least for 72 h. Alendronate did not change OPG expression in basal, 10% fetal bovine serum (FBS), and vitamin D-treated cultures. Similar results were observed at the protein level. Unexpectedly, alendronate at 10−7 and 10−5 M concentrations increased the RANKL expression with the presence of vitamin D in differentiated hOB, and this induction of RANKL mRNA levels by alendronate was dose-dependent. However, this effect was not observed in basal and 10% FBS culture conditions. Thus, we conclude that alendronate does not affect the ALP activity and OPG gene expression in differentiated hOB, but may increase RANKL gene expression induced by vitamin D.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. R.G. Russell, N.B. Watts, F.H. Ebetino, M.J. Rogers, Osteoporos. Int. 19, 733–759 (2008)

    Article  CAS  PubMed  Google Scholar 

  2. M.J. Rogers, Curr. Pharm. Des. 9, 2643–2658 (2003)

    Article  CAS  PubMed  Google Scholar 

  3. J.E. Dunford, K. Thompson, F.P. Coxon, S.P. Luckman, F.M. Hahn, C.D. Poulter, F.H. Ebetino, M.J. Rogers, J. Pharmacol. Exp. Ther. 296, 235–242 (2001)

    CAS  PubMed  Google Scholar 

  4. J.E. Dunford, M.J. Rogers, F.H. Ebetino, R.J. Phipps, F.P. Coxon, J. Bone Miner. Res. 21, 684–694 (2006)

    Article  PubMed  Google Scholar 

  5. S.P. Luckman, D.E. Hughes, F.P. Coxon, R. Graham, G. Russell, M.J. Rogers, J. Bone Miner. Res. 13, 581–589 (1998)

    Article  CAS  PubMed  Google Scholar 

  6. E. van Beek, E. Pieterman, L. Cohen, C. Lowik, S. Papapoulos, Biochem. Biophys. Res. Commun. 264, 108–111 (1999)

    Article  PubMed  Google Scholar 

  7. E.R. Van Beek, C.W. Lowik, S.E. Papapoulos, Bone 30, 64–70 (2002)

    Article  PubMed  Google Scholar 

  8. G.H. Nancollas, R. Tang, R.J. Phipps, Z. Henneman, S. Gulde, W. Wu, A. Mangood, R.G. Russell, F.H. Ebetino, Bone 38, 617–627 (2006)

    Article  CAS  PubMed  Google Scholar 

  9. A.I. Idris, J. Rojas, I.R. Greig, R.J. Van’t Hof, S.H. Ralston, Calcif. Tissue Int. 82, 191–201 (2008)

    Article  CAS  PubMed  Google Scholar 

  10. U.A. Liberman, S.R. Weiss, J. Broll, H.W. Minne, H. Quan, N.H. Bell, J. Rodriguez-Portales, R.W. Jr. Downs, J. Dequeker, M. Favus, N. Engl. J. Med. 333, 1437–1443 (1995)

    Article  CAS  PubMed  Google Scholar 

  11. D.M. Black, D.E. Thompson, D.C. Bauer, K. Ensrud, T. Musliner, M.C. Hochberg, M.C. Nevitt, S. Suryawanshi, S.R. Cummings, J. Clin. Endocrinol. Metab. 85, 4118–4124 (2000)

    Article  CAS  PubMed  Google Scholar 

  12. A. Cranney, G. Wells, A. Willan, L. Griffith, N. Zytaruk, V. Robinson, D. Black, J. Adachi, B. Shea, P. Tugwell, G. Guyatt, Osteoporosis Methodology Group and The Osteoporosis Research Advisory Group, Endocr. Rev. 23, 508–516 (2002)

    Article  CAS  PubMed  Google Scholar 

  13. E. Engel, S. Serrano, M.L. Marinoso, J. Lloreta, F. Ulloa, X. Nogués, A. Diez-Pérez, J. Carbonell, Calcif. Tissue Int. 72, 228–235 (2003)

    Article  CAS  PubMed  Google Scholar 

  14. Y.H. Kim, G.S. Kim, B. Jeong-Hwa, Exp. Mol. Med. 34, 145–151 (2002)

    CAS  PubMed  Google Scholar 

  15. V. Viereck, G. Emons, V. Lauck, K.H. Frosch, S. Blaschke, C. Gründker, L.C. Hofbauer, Biochem. Biophys. Res. Commun. 291, 680–686 (2002)

    Article  CAS  PubMed  Google Scholar 

  16. C. Vitte, H. Fleisch, H.L. Guenther, Endocrinology 137, 2324–2333 (1996)

    Article  CAS  PubMed  Google Scholar 

  17. B.F. Boyce, L. Xing, Arch. Biochem. Biophys. 473, 139–146 (2008)

    Article  CAS  PubMed  Google Scholar 

  18. A.E. Kearns, S. Khosla, P.J. Kostenuik, Endocr. Rev. 29, 155–192 (2008)

    Article  CAS  PubMed  Google Scholar 

  19. M.C. Walsh, Y. Choi, Cytokine Growth Factor Rev. 14, 251–263 (2003)

    Article  CAS  PubMed  Google Scholar 

  20. O. Fromigue, J.J. Body, J. Endocrinol. Invest. 25, 539–546 (2002)

    CAS  PubMed  Google Scholar 

  21. L. Fu, T. Tang, Y. Miao, S. Zhang, Z. Qu, K. Dai, Bone 43, 40–47 (2008)

    Article  CAS  PubMed  Google Scholar 

  22. C. Garcia-Moreno, S. Serrano, M. Nacher, M. Farré, A. Díez, M.L. Mariñoso, J. Carbonell, L. Mellibovsky, X. Nogués, J. Ballester, J. Aubía, Bone 22, 233–239 (1998)

    Article  CAS  PubMed  Google Scholar 

  23. N. Giuliani, M. Pedrazzoni, G. Negri, G. Passeri, M. Impicciatore, G. Girasole, Bone 22, 455–461 (1998)

    Article  CAS  PubMed  Google Scholar 

  24. G.I. Im, S.A. Qureshi, J. Kenney, H.E. Rubash, A.S. Shanbhag, Biomaterials 25, 4105–4115 (2004)

    Article  CAS  PubMed  Google Scholar 

  25. F. Itoh, S. Aoyagi, H. Furihata-Komatsu, M. Aoki, H. Kusama, M. Kojima, H. Kogo, Eur. J. Pharmacol. 477, 9–16 (2003)

    Article  CAS  PubMed  Google Scholar 

  26. G.G. Reinholz, B. Getz, L. Pederson, E.S. Sanders, M. Subramaniam, J.N. Ingle, T.C. Spelsberg, Cancer Res. 60, 6001–6007 (2000)

    CAS  PubMed  Google Scholar 

  27. I. Mathov, L.I. Plotkin, C.L. Sgarlata, J. Leoni, T. Bellido, J. Bone Miner. Res. 16, 2050–2056 (2001)

    Article  CAS  PubMed  Google Scholar 

  28. G. Duque, D. Rivas, J. Bone Miner. Res. 22, 1603–1611 (2007)

    Article  CAS  PubMed  Google Scholar 

  29. Y. Abe, A. Kawakami, T. Nakashima, E. Ejima, K. Fujiyama, T. Kiriyama, A. Ide, N. Sera, T. Usa, T. Tominaga, K. Ashizawa, N. Yokoyama, K. Eguchi, J. Lab. Clin. Med. 136, 344–354 (2000)

    Article  CAS  PubMed  Google Scholar 

  30. A. Naidu, P.C. Dechow, R. Spears, J.M. Wright, H.P. Kessler, L.A. Opperman, Oral Surg. Oral Med. Oral Pathol. Oral Radiol. Endod. 106, 5–13 (2008)

    Article  PubMed  Google Scholar 

  31. L.I. Plotkin, T. Bellido, Cell Adhes. Commun. 8, 377–382 (2001)

    Article  CAS  Google Scholar 

  32. L.I. Plotkin, S.C. Manolagas, T. Bellido, Bone 39, 443–452 (2006)

    Article  CAS  PubMed  Google Scholar 

  33. L.I. Plotkin, R.S. Weinstein, A.M. Parfitt, P.K. Roberson, S.C. Manolagas, T. Bellido, J. Clin. Invest. 104, 1363–1374 (1999)

    Article  CAS  PubMed  Google Scholar 

  34. L. Gomez-Garcia, P. Esbrit, L. Carreno, P. Sabando, M. García-Flores, M.E. Martinez, J. Bone Miner. Res. 18, 78–87 (2003)

    Article  CAS  PubMed  Google Scholar 

  35. J.L. Sanders, G. Tarjan, S.A. Foster, P.H. Stern, J. Bone Miner. Res. 13, 786–792 (1998)

    Article  CAS  PubMed  Google Scholar 

  36. M.H. Yun, J.S. Woo, K.I. Kwon, Arch. Pharm. Res. 29, 328–332 (2006)

    Article  CAS  PubMed  Google Scholar 

  37. P.G. Robey, J.D. Termine, Calcif. Tissue Int. 37, 453–460 (1985)

    Article  CAS  PubMed  Google Scholar 

  38. M.V. Hernandez, N. Guanabens, L. Alvarez, A. Monegal, P. Peris, J. Riba, G. Ercilla, M.J. Martínez de Osaba, J. Muñoz-Gómez, Calcif. Tissue Int. 74, 284–293 (2004)

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

This study was supported by a grant from the Spanish Ministerio de Ciencia y Tecnología (PIO50044 and C03/02), and the Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd) (C03/08).

Author information

Authors and Affiliations

  1. Metabolic Bone Diseases Unit, Department of Rheumatology, Hospital Clinic-IDIBAPS, University of Barcelona, Barcelona, Spain

    Anna Enjuanes, Silvia Ruiz-Gaspà, Pilar Peris, Dolores Ozalla, Luisa Álvarez, Andrés Combalia, M. Jesús Martínez de Osaba, Ana Monegal & Nuria Guañabens

  2. Centro de Investigaciones Biomédicas en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Hospital Clinic-IDIBAPS, University of Barcelona, Barcelona, Spain

    Silvia Ruiz-Gaspà, Pilar Peris, Luisa Álvarez, M. Jesús Martínez de Osaba, Albert Pares & Nuria Guañabens

  3. Liver Unit, Hospital Clinic-IDIBAPS, University of Barcelona, Barcelona, Spain

    Albert Pares

Authors
  1. Anna Enjuanes
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Silvia Ruiz-Gaspà
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Pilar Peris
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Dolores Ozalla
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Luisa Álvarez
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Andrés Combalia
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. M. Jesús Martínez de Osaba
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Ana Monegal
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Albert Pares
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Nuria Guañabens
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Anna Enjuanes.

Additional information

Anna Enjuanes and Silvia Ruiz-Gaspà contributed equally to this study.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Enjuanes, A., Ruiz-Gaspà, S., Peris, P. et al. The effect of the alendronate on OPG/RANKL system in differentiated primary human osteoblasts. Endocr 37, 322–328 (2010). https://doi.org/10.1007/s12020-009-9306-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12020-009-9306-8

Keywords

Search

Navigation