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

Kong, Young-Yun
Yoshida, Hiroki
Sarosi, Ildiko
Tan, Hong-Lin
Timms, Emma
Capparelli, Casey
Morony, Sean
Oliveira-dos-Santos, Antonio J.
Van, Gwyneth
Itie, Annick
Khoo, Wilson
Wakeham, Andrew
Dunstan, Colin R.
Lacey, David L.
Mak, Tak W.
Boyle, William J.
Penninger, Josef M.

(Kong, Yoshida, Oliveira-dos-Santos, Itie, Khoo, Wakeham, Mak, Penninger) Amgen Institute, Ontario Cancer Institute, and the Departments of Medical Biophysics and Immunology, University of Toronto, 620 University Avenue, Toronto, Ontario M5G 2C1, Canada
Departments of (Sarosi, Tan, Capparelli, Morony, Van, Dunstan) Pathology and (Timms, Lacey, Boyle) Cell Biology, Amgen Inc., One Amgen Center Drive, Thousand Oaks, California 91320-1789, USA

Nature 397(6717):p 315-323, January 28, 1999.

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.