Article

Nature 397, 315-323 (28 January 1999) | doi:10.1038/16852; Received 1 October 1998; Accepted 4 December 1998

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

Young-Yun Kong1, Hiroki Yoshida1, Ildiko Sarosi2, Hong-Lin Tan2, Emma Timms3, Casey Capparelli2, Sean Morony2, Antonio J. Oliveira-dos-Santos1, Gwyneth Van2, Annick Itie1, Wilson Khoo1, Andrew Wakeham1, Colin R. Dunstan2, David L. Lacey3, Tak W. Mak1, William J. Boyle3 & Josef M. Penninger1

  1. Amgen Institute, Ontario Cancer Institute, and the Departments of Medical Biophysics and Immunology, University of Toronto, 620 University Avenue, Toronto, Ontario M5G 2C1, Canada
  2. Departments of Pathology, Amgen Inc., One Amgen Center Drive, Thousand Oaks, California 91320-1789, USA
  3. Departments of Cell Biology, Amgen Inc., One Amgen Center Drive, Thousand Oaks, California 91320-1789, USA

Correspondence to: Josef M. Penninger1 Correspondence and requests for materials should be addressed to J.M.P. (e-mail: Email: jpenning@amgen.com).

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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.