The HIV protease inhibitor ritonavir blocks osteoclastogenesis and function by impairing RANKL-induced signaling
J. Clin. Invest. Michael W.-H. Wang, et al. 114:206 doi:10.1172/JCI15797 [Go to this article.]

Figure 5
Ritonavir inhibits RANKL-induced NF-κB activation. (A) Bone marrow macrophages pretreated with ritonavir (20 μg/ml) or vehicle for 1 hour were stimulated with RANKL for the indicated time points, and protein lysates were prepared for IκBα immunoblot. Ritonavir pretreatment impairs RANKL-induced degradation of IκBα. (B) Bone marrow macrophages pretreated with ritonavir (20 μg/ml) for the indicated time were stimulated with RANKL for 15 minutes and evaluated for NF-κB activation. Ritonavir inhibits NF-κB activation as assessed by EMSA after 1 hour and after 18 hours of pretreatment (Pretx). Numbers below lanes indicate relative band intensity. (C) Cell lysates prepared as in A and immunoblotted for phospho-IκBα (p-IκBα) and IκBα reveal similar levels of phospho-IκBα intensity, irrespective of ritonavir pretreatment, despite the failure of ritonavir pretreatment to decrease total IκBα levels. β-Actin immunoblots confirm similar amounts of cell extracts were analyzed.