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 6
Ritonavir inhibits RANKL-induced Akt activation. (A) RAW 264.7 cells pretreated with ritonavir (2 μg/ml) for 1 hour and stimulated with RANKL (+RANKL) for the indicated time points. Phospho-Akt (p-Akt), total Akt (Akt), and phospho-FKHR (p-FKHR) immunoblots were performed on cell extracts. Immunoblots reveal impaired Akt and FKHR phosphorylation with ritonavir pretreatment. (B) Osteoclasts were stimulated with either RANKL or M-CSF for the indicated time points, and cell extracts were immunoblotted for Akt activation. Ritonavir inhibits only RANKL-induced Akt activation but not that stimulated by M-CSF. Total Akt immunoblots confirm that similar amounts of cell extracts were analyzed. +V, vehicle pretreatment; +R, ritonavir pretreatment.