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

Department of Cytokine Biology, Forsyth Institute & Harvard School of Dental Medicine, Boston, MA 02135, USA

W. Chen

Department of Cytokine Biology, Forsyth Institute & Harvard School of Dental Medicine, Boston, MA 02135, USA

Y.-P. Li

Department of Cytokine Biology, Forsyth Institute & Harvard School of Dental Medicine, Boston, MA 02135, USA, Harvard-Forsyth Department of Oral Biology, Forsyth Institute & Harvard School of Dental Medicine, Boston, MA 02135, USA, ypli{at}forsyth.org

The cytokine, IFN-, 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- may inhibit bone resorption through down-regulation of osteoclast genes, including cathepsin K. To test the hypothesis, we investigated the effect of IFN- 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- down-regulates mRNA levels of cathepsin K in a time- and dose-dependent manner. Consequently, cathepsin K protein production is also reduced by IFN-. Moreover, our results indicate that IFN- 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- 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.

Key Words: interferon-gamma • cathepsin K • osteoclast formation • gene regulation

Journal of Dental Research, Vol. 80, No. 1, 351-355 (2001)
DOI: 10.1177/00220345010800011001


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