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IL-7 induces bone loss in vivo by induction of receptor activator of nuclear factor κB ligand and tumor necrosis factor α from T cells

2002; National Academy of Sciences; Volume: 100; Issue: 1 Linguagem: Inglês

10.1073/pnas.0136772100

1091-6490

Gianluca Toraldo, Cristiana Roggia, Weiping Qian, Roberto Pacifici, M. Neale Weitzmann,

NF-κB Signaling Pathways

IL-7, a powerful lymphopoietic cytokine, is elevated in rheumatoid arthritis (RA) and known to induce bone loss when administered in vivo . IL-7 has been suggested to induce bone loss, in part, by stimulating the proliferation of B220 + cells, a population capable of acting as early osteoclast (OC) precursors. However, the mechanism by which IL-7 leads to differentiation of precursors into mature OCs remains unknown. We previously reported that, in vitro , IL-7 up-regulated T cell cytokines including receptor activator of nuclear factor κB ligand (RANKL). To demonstrate the importance of T cells to the bone-wasting effect of IL-7 in vivo , we have now examined IL-7-induced bone loss in T cell-deficient nude mice. We show that T cell-replete mice undergo significant osteoclastic bone loss after IL-7 administration, concurrent with induction of RANKL and tumor necrosis factor α (TNF-α) secretion by splenic T cells. In contrast, nude mice were resistant to IL-7-induced bone loss and showed no detectable increase in either RANKL or TNF-α, despite an up-regulation of B220 + cells. Importantly, T cell adoptive transfer into nude mice restored IL-7-induced bone loss, and RANKL and TNF-α secretion, demonstrating that T cells are essential mediators of IL-7-induced bone loss in vivo .