LAUSR

&NA; [4‐(acetylamino)‐N‐(2‐amino‐phenyl) benzamide] (CI‐994) is a histone deacetylase 1‐3 specific inhibitor that has been shown to indirectly increase the production of Dickkopf‐1, which is an inhibitor of osteoclastic development. However, whether CI‐994 has an influence on receptor activator of nuclear factor‐kappa B ligand (RANKL)‐induced osteoclastogenesis is still unclear; in our study, this mechanism was investigated. In an in vitro study, using a tartrate‐resistant acid phosphatase (TRAP) stain, an F‐actin ring, bone absorption test, quantitative PCR and Western blotting, the role of CI‐994 in osteoclastogenesis and the expression of related genes and proteins were investigated. In an in vivo study, the effect of CI‐994 on osteolysis was evaluated using a titanium particle‐induced murine calvarial osteolysis model. Our results indicated that CI‐994 inhibited osteoclast differentiation and the function of bone resorption without cytotoxic effects. Moreover, CI‐994 inhibited the expression of osteoclast‐related genes, including ACP5, CTSK, NFATc1, c‐Fos, DC‐STAMP and V‐ATPase‐d2. Furthermore, CI‐994 suppressed the phosphorylation of I&kgr;B&agr; and p65 and the expression of downstream c‐Fos and NFATc1. Consistent with the in vitro results described above, our in vivo experiment indicated that CI‐994 inhibited Ti‐induced osteolysis. In conclusion, CI‐994 inhibited osteoclastogenesis by suppressing NF‐&kgr;B and the downstream c‐Fos/NFATc1 signaling pathway. Thus, this study showed the possibility of using CI‐994 for the treatment of exorbitant osteoclastic bone resorption.