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OPGL is a key regulator of osteoclastogenesis, lymphocyte development and lymph-node organogenesis

Nature volume 397, pages 315–323 (1999)Cite this article

Abstract

The tumour-necrosis-factor-family molecule osteoprotegerin ligand (OPGL; also known as TRANCE, RANKL and ODF) has been identified as a potential osteoclast differentiation factor and regulator of interactions between T cells and dendritic cells in vitro. Mice with a disrupted opgl gene show severe osteopetrosis and a defect in tooth eruption, and completely lack osteoclasts as a result of an inability of osteoblasts to support osteoclastogenesis. Although dendritic cells appear normal, opgl-deficient mice exhibit defects in early differentiation of T and B lymphocytes. Surprisingly, opgl-deficient mice lack all lymph nodes but have normal splenic structure and Peyer's patches. Thus OPGL is a new regulator of lymph-node organogenesis and lymphocyte development and is an essential osteoclast differentiation factor in vivo.

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Figure 1: Targeting of the opgl gene.
Figure 2: Osteopetrosis and absence of osteoclasts in opgl−/− mice.
Figure 3: opgl−/− mice show normal osteoclast precursors but an inability of osteoblasts to support osteoclastogenes.
Figure 4: Impaired lymphocyte development in opgl−/− mice.
Figure 5: OPGL regulates lymph-node organogenesis.

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Acknowledgements

We thank D. Bouchard for cell sorting; D. Duryea and C. Burgh for technical assistance; R. Boyd, M. Bachmann, G. Wick, and N.Romani for reagents; M. Saunders for editing this manuscript; and R. Yoshida, K. Bachmaier, A.Hakem, I.Kozieradzki, T. Sasaki and M. Nghiem for comments.

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Authors and Affiliations

  1. Amgen Institute, and the Departments of Medical Biophysics and Immunology, Ontario Cancer Institute, University of Toronto, 620 University Avenue, Toronto, M5G 2C1, Ontario, Canada

    Young-Yun Kong, Hiroki Yoshida, Antonio J. Oliveira-dos-Santos, Annick Itie, Wilson Khoo, Andrew Wakeham, Tak W. Mak & Josef M. Penninger

  2. Departments of Pathology, Amgen Inc., One Amgen Center Drive, Thousand Oaks, 91320-1789, California, USA

    Ildiko Sarosi, Hong-Lin Tan, Casey Capparelli, Sean Morony, Gwyneth Van & Colin R. Dunstan

  3. Departments of Cell Biology, Amgen Inc., One Amgen Center Drive, Thousand Oaks, 91320-1789, California, USA

    Emma Timms, David L. Lacey & William J. Boyle

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Correspondence to Josef M. Penninger.

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Kong, YY., Yoshida, H., Sarosi, I. et al. OPGL is a key regulator of osteoclastogenesis, lymphocyte development and lymph-node organogenesis. Nature 397, 315–323 (1999). https://doi.org/10.1038/16852

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