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

Bone remodelling and bone loss are controlled by a balance between the tumo ur necrosis factor family molecule osteoprotegerin ligand (OPGL) and its de coy receptor osteoprotegerin (OPG)(1-3). In addition, OPGL regulates lymph node organogenesis, lymphocyte development and interactions between T cells and dendritic cells in the immune system(3-5). The OPGL receptor, RANK, is expressed on chondrocytes, osteoclast precursors and mature osteoclasts(4, 6). OPGL expression in T cells is induced by antigen receptor engagement(7) , which suggests that activated T cells may influence bone metabolism throu gh OPGL and RANK. Here we report that activated T cells can directly trigge r osteoclastogenesis through OPGL. Systemic activation of T cells in vivo l eads to an OPGL-mediated increase in osteoclastogenesis and bone loss. In a T-cell-dependent model of rat adjuvant arthritis characterized by severe j oint inflammation, bone and cartilage destruction and crippling, blocking o f OPGL through osteoprotegerin treatment at the onset of disease prevents b one 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 regu lators of bone physiology.