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

Kong, Young-Yun<sup>1</sup>; Yoshida, Hiroki<sup>1</sup>; Sarosi, Ildiko<sup>2</sup>; Tan, Hong-Lin<sup>2</sup>; Timms, Emma<sup>3</sup>; Capparelli, Casey<sup>2</sup>; Morony, Sean<sup>2</sup>; Oliveira-dos-Santos, Antonio J.<sup>1</sup>; Van, Gwyneth<sup>2</sup>; Itie, Annick<sup>1</sup>; Khoo, Wilson<sup>1</sup>; Wakeham, Andrew<sup>1</sup>; Dunstan, Colin R.<sup>2</sup>; Lacey, David L.<sup>3</sup>; Mak, Tak W.<sup>1</sup>; Boyle, William J.<sup>3</sup>; Penninger, Josef M.<sup>1</sup>

Affiliations

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

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

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

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.

Links

DOI: 10.1038/16852

PubMed: 9950424

WoS: 000078324600040

History

Received: 1998-10-01

Accepted: 1998-12-04

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