Activated T cells regulate bone loss and joint destruction in adjuvant arthritis through osteoprotegerin ligand (original) (raw)

Nature volume 402, pages 304–309 (1999)Cite this article

Abstract

Bone remodelling and bone loss are controlled by a balance between the tumour necrosis factor family molecule osteoprotegerin ligand (OPGL) and its decoy receptor osteoprotegerin (OPG)1,2,3. In addition, OPGL regulates lymph node organogenesis, lymphocyte development and interactions between T cells and dendritic cells in the immune system3,4,5. The OPGL receptor, RANK, is expressed on chondrocytes, osteoclast precursors and mature osteoclasts4,6. OPGL expression in T cells is induced by antigen receptor engagement7, which suggests that activated T cells may influence bone metabolism through OPGL and RANK. Here we report that activated T cells can directly trigger osteoclastogenesis through OPGL. Systemic activation of T cells in vivo leads to an OPGL-mediated increase in osteoclastogenesis and bone loss. In a T-cell-dependent model of rat adjuvant arthritis characterized by severe joint inflammation, bone and cartilage destruction and crippling, blocking of OPGL through osteoprotegerin treatment at the onset of disease prevents bone and cartilage destruction but not inflammation. These results show that both systemic and local T-cell activation can lead to OPGL production and subsequent bone loss, and they provide a novel paradigm for T cells as regulators of bone physiology.

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Acknowledgements

We thank E. C. Keystone for providing patient samples and C. Dunstan for critical comments. Technical assistance was provided by Y. Cheng, E. Julian, C. Burgh, A. Shahinian and D. Duryea. We are grateful to M. E. Saunders for scientific editing and A. Hessel, A. Oliveira dos Santos, K. Bachmaier, T. Sasaki and all other members of the laboratory for comments.

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Author notes

  1. Young-Yun Kong, Ulrich Feige, Linh T. Nguyen, Pamela S. Ohashi and Josef M. Penninger: These authors contributed equally to this work

Authors and Affiliations

  1. Amgen Institute, 620 University Avenue, Toronto, M5G 2C1, Ontario, Canada
    Young-Yun Kong, Anna Tafuri & Josef M. Penninger
  2. Department of Pharmacology,
    Ulrich Feige & Giuseppe Campagnuolo
  3. Pathology, and,
    Iidiko Sarosi, Brad Bolon, Sean Morony, Casey Capparelli, Gwyneth Van & David L. Lacey
  4. Cell Biology, Amgen Inc., One Amgen Center Drive, Thousand Oaks, 91320-1789, California, USA
    Ji Li, Robin Elliott, Susan McCabe & William J. Boyle
  5. Department of Medical Genetics & Microbiology,
    Thomas Wong & Eleanor Fish
  6. St Michael's Hospital,
    Erika Moran & Earl R. Bogoch
  7. Ontario Cancer Institute and the Departments of Medical Biophysics and Immunology, University of Toronto, Toronto, Ontario, Canada
    Linh T. Nguyen, Pamela S. Ohashi & Josef M. Penninger

Authors

  1. Young-Yun Kong
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  2. Ulrich Feige
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  3. Iidiko Sarosi
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  4. Brad Bolon
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  5. Anna Tafuri
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  6. Sean Morony
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  7. Casey Capparelli
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  8. Ji Li
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  9. Robin Elliott
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  10. Susan McCabe
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  11. Thomas Wong
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  12. Giuseppe Campagnuolo
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  13. Erika Moran
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  14. Earl R. Bogoch
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  15. Gwyneth Van
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  16. Linh T. Nguyen
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  17. Pamela S. Ohashi
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  18. David L. Lacey
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  19. Eleanor Fish
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  20. William J. Boyle
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  21. Josef M. Penninger
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Kong, YY., Feige, U., Sarosi, I. et al. Activated T cells regulate bone loss and joint destruction in adjuvant arthritis through osteoprotegerin ligand.Nature 402, 304–309 (1999). https://doi.org/10.1038/46303

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