IFN-gamma Tips Towards Bone Destruction

The soluble factor IFN-gamma has been shown to both promote and inhibit bone destruction, but the mechanisms by which it mediates these opposing effects and which effect predominates in vivo have not been clearly established.

Using mice, researchers from Emory University have shown that in vitro, IFN-gamma directly inhibits the differentiation of cells that destroy bone (osteoclasts) and indirectly promotes their differentiation. In this study, which appears online in advance of publication in the January print issue of the Journal of Clinical Investigation, Roberto Pacifici and colleagues further demonstrated that the in vitro indirect effects of IFN-gamma were a result of this soluble factor increasing the activity of APCs, thereby increasing T cell activation and production of the pro-osteoclastogenic factors RANKL and TNF-alpha. Importantly, the bone destroying effects of IFN-gamma were found to predominate in vivo in 3 distinct models of bone loss (osteoporosis). It is therefore possible that targeting IFN-gamma might provide a new approach to prevent bone loss in individuals with osteoporosis.(Source: Journal of Clinical Investigation : Emory University : January 2007.)