PMID:12490655

Citation	Toraldo, G, Roggia, C, Qian, WP, Pacifici, R and Weitzmann, MN (2003) IL-7 induces bone loss in vivo by induction of receptor activator of nuclear factor kappa B ligand and tumor necrosis factor alpha from T cells. Proc. Natl. Acad. Sci. U.S.A. 100:125-30
Abstract	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 kappaB 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 alpha (TNF-alpha) 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-alpha, 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-alpha secretion, demonstrating that T cells are essential mediators of IL-7-induced bone loss in vivo.
Links	PubMed PMC140902 Online version:10.1073/pnas.0136772100
Keywords	Adoptive Transfer; Animals; Bone Resorption/chemically induced; Bone Resorption/immunology; Bone Resorption/pathology; Carrier Proteins/metabolism; Cells, Cultured; Glycoproteins/metabolism; Interleukin-7/pharmacology; Lymphocyte Transfusion; Membrane Glycoproteins/metabolism; Mice; Mice, Nude; NF-kappa B/metabolism; Osteoclasts/immunology; Osteoprotegerin; RANK Ligand; Receptor Activator of Nuclear Factor-kappa B; Receptors, Cytoplasmic and Nuclear/metabolism; Receptors, Tumor Necrosis Factor/metabolism; T-Lymphocytes/immunology; T-Lymphocytes/pathology; Tumor Necrosis Factor-alpha/immunology
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