Ifn-gamma Stimulates Osteoclast Formation and Bone Loss in Vivo Via Antigen-driven T Cell Activation.
From: Division of Endocrinology, Metabolism and Lipids, Department of Medicine, Emory University, Atlanta, Georgia 30322, USA.
The Journal of clinical investigation
- Publish Date: Jan 2007
- ISSN: 0021-9738
- Volume: 117
- Issue: 1
- Pages: 122-32
- Medium: Print
- Language: English
- Citation (JAMA): Gao Yuhao, Grassi Francesco, Ryan Michaela Robbie, et al. Ifn-gamma Stimulates Osteoclast Formation and Bone Loss in Vivo Via Antigen-driven T Cell Activation.. J. Clin. Invest. Jan 2007;117:122-32
Abstract
T cell-produced cytokines play a pivotal role in the bone loss caused by inflammation, infection, and estrogen deficiency. IFN-gamma is a major product of activated T helper cells that can function as a pro- or antiresorptive cytokine, but the reason why IFN-gamma has variable effects in bone is unknown. Here we show that IFN-gamma blunts osteoclast formation through direct targeting of osteoclast precursors but indirectly stimulates osteoclast formation and promotes bone resorption by stimulating antigen-dependent T cell activation and T cell secretion of the osteoclastogenic factors RANKL and TNF-alpha. Analysis of the in vivo effects of IFN-gamma in 3 mouse models of bone loss - ovariectomy, LPS injection, and inflammation via silencing of TGF-beta signaling in T cells - reveals that the net effect of IFN-gamma in these conditions is that of stimulating bone resorption and bone loss. In summary, IFN-gamma has both direct anti-osteoclastogenic and indirect pro-osteoclastogenic properties in vivo. Under conditions of estrogen deficiency, infection, and inflammation, the net balance of these 2 opposing forces is biased toward bone resorption. Inhibition of IFN-gamma signaling may thus represent a novel strategy to simultaneously reduce inflammation and bone loss in common forms of osteoporosis.
Mesh Headings (Keywords): Alveolar Bone Loss, Animals, Antigens, Interferon Type II, Lymphocyte Activation, Mice, Models, Animal, Osteoclasts, RANK Ligand, Recombinant Proteins, T-Lymphocytes
Check for Full Text / PubMed Unique Identifier (PMID): 17173138
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