Interferon-γ Down-regulates Gene Expression of Cathepsin K in Osteoclasts and Inhibits Osteoclast Formation

Abstract

The cytokine, IFN-γ, has been shown in vitro to inhibit bone resorption, but the mechanisms responsible for this inhibition have not been clearly defined. Cathepsin K is a major protease responsible for bone resorption. IFN-γ may inhibit bone resorption through down-regulation of osteoclast genes, including cathepsin K. To test the hypothesis, we investigated the effect of IFN-γ on cathepsin K expression in the MOCP-5 and wild-type mouse bone marrow co-culture systems by Northern blot as well as osteoclast formation at different stages of differentiation. The results show that IFN-γ down-regulates mRNA levels of cathepsin K in a time- and dose-dependent manner. Consequently, cathepsin K protein production is also reduced by IFN-γ. Moreover, our results indicate that IFN-γ inhibits osteoclast formation only early in osteoclast differentiation. IL-6 and TNFa did not significantly affect cathepsin K gene expression in osteoclasts. However, IL-la stimulated gene expression. In conclusion, our data suggest that the actions of IFN-γ on osteoclastic bone resorption may be mediated by its effects on both osteoclast formation at an early stage and osteoclast gene expression in mature osteoclasts.