Interferon-g down-regulates gene expression of cathepsin K in osteoclasts and inhibit osteoclast formation

Suttatip Kamolmatyakul, D. of Preventive Dentistry, F. of Dentistry, PSU.
Wei Chen, D. of Medicine, Forsyth Inst., Boston, USA.
Yi-Ping Li, Assoc. Prof., Member of Staff, Forsyth Inst., Boston, USA.
Corresponding e-mail : ypli@forsyth.org

Grant : DE-10887 from the NIDR, USA
Presented : The Edward H. Hatton Award competition, the 77th general session of the International Association for Dental Research, 10-13 March 1999 Vancouver, Canada
Key words : interferon-gamma, cathepsin K, osteoclast

Cathepsin K is recently identified lysosomal cystein proteinase of papain family closely related to cathepsin L and S. It is regarded as a key protease responsible for bone resorption and remodeling. Cathepsin K was found to be abundantly and selectively expressed in osteoclasts. Interferon-g (IFN-g) is a glycoprotein produced by activated lymphocyte and natural killer cells and has multiple bio- logic efffects, including antiviral, antitumor, and cell growth inhibitory activities. Like many other cytokines, IFN-g also has function in bone metabolism. It inhibits osteoclastic bone resorption, but the mechanism responsible for this inhibition is unknown. In the present study, the effect of IFN-g on cathepsin K expression was determined in MOCP-5 and MS-12 co-culture system. This system, recently generated in our laboratory, has been proven to be a useful model for the study of osteoclast formation, osteoclast-expressed gene regulation, and osteoclast function (J. Bone Mine. Res. 13: 1112-1123, 1998). MOCP-5 cells were co-culture with MS-12 cells in 6-well plate with minimum essential media (MEM) and 10 % fetal calf serum at 37oC and 5% CO2. IFN-g was added at various dose when MOCP-5 cells fully differentiated into osteoclasts on day 5th. IFN-g was not added to controls. Cells were then harvested at various time. Northern Blot Analysis was carried out. The results show that IFN-g down-regulates the mRNA levels of cathepsin K in dose-responsive and time-dependent manner. This inhibitory effect was enhanced when added in conjunction with Dexamethasone. 1, 25-dihydroxyvitamin D3 also enhanced this effect, but was not as strong as Dexamethasone. However IFN-g shows no discernible effects on osteoclast formation by tartrate-resistant acid phosphatase (TRAP) staining assay in MOPC-5 and MS-12 co-culture system. Hence we conclude that the actions of IFN-g on osteoclastic bone resorption may be mediated by its effects on down-regulation of cathepsin K expression. This study was supported by the grant DE- 10887 from the NIDR

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