/On the other hand, the osteoclastogenic effect of Hottip was examined and it was found the bigger and mature osteoclasts in MNCs derived from Hottip KO mice by TRAP staining. Their bone resorption was strongly promoted as well. Conversely, Hottip overexpression suppressed osteoclastogenic differentiation and bone resorption. Considering that F-actin ring formation plays a critical role in osteoclastic bone resorption, we investigated the influence of Hottip on F-actin ring formation. As shown in, Hottip knockout stimulated while its overexpression inhibited F-actin ring formation in osteoclasts. Furthermore, several crucial genes related to osteoclast differentiation such as CTSK, TRAP, β3-intergrin, Atp6v0d2, Arg-1, BCL-6, dc-stamp, NF-κB and RANKL were examined and the results showed that they were significantly promoted by Hottip knockout while obviously suppressed by Hottip overexpression. Taken together, these results suggest that Hottip possibly serves as an negative regulator of osteoclast differentiation and bone resorption.