Activated T cells regulate bone loss and joint destruction in adjuvant arthritis through osteoprotegerin ligand

Young-Yun Kong, Ulrich Feige, Iidiko Sarosi, Brad Bolon, Anna Tafuri, Sean Morony, Casey Capparelli, Ji Li, Robin Elliott, Susan McCabe, Thomas Wong, Giuseppe Campagnuolo, Erika Moran, Earl R. Bogoch, Gwyneth Van, Linh T. Nguyen, Pamela S. Ohashi, David L. Lacey, Eleanor Fish, William J. Boyle and Josef M. Penninger
Additional contact information
Young-Yun Kong: Amgen Institute
Ulrich Feige: Department of Pharmacology
Iidiko Sarosi: Pathology, and
Brad Bolon: Pathology, and
Anna Tafuri: Amgen Institute
Sean Morony: Pathology, and
Casey Capparelli: Pathology, and
Ji Li: Cell Biology, Amgen Inc.
Robin Elliott: Cell Biology, Amgen Inc.
Susan McCabe: Cell Biology, Amgen Inc.
Thomas Wong: Department of Medical Genetics & Microbiology
Giuseppe Campagnuolo: Department of Pharmacology
Erika Moran: St Michael's Hospital
Earl R. Bogoch: St Michael's Hospital
Gwyneth Van: Pathology, and
Linh T. Nguyen: University of Toronto
Pamela S. Ohashi: University of Toronto
David L. Lacey: Pathology, and
Eleanor Fish: Department of Medical Genetics & Microbiology
William J. Boyle: Cell Biology, Amgen Inc.
Josef M. Penninger: Amgen Institute

Nature, 1999, vol. 402, issue 6759, 304-309

Abstract: 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.

Date: 1999
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DOI: 10.1038/46303

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