Abstract: AimTo study the inhibitory action of diacerein on the formation of osteoclasts (OCLs) and their activity in bone resorption as well as the relationship between this action and the expression of osteoprotegerin (OPG) and receptor activator of NF-κB ligand (RANKL) in MC3T3-E1 cells. Methods A coculture system constituted with MC3T3-E1 cells and bone marrow cells for osteoclasts formation was established in vitro. TRAP-positive and multinucleated cells with three or more nuclei in each cell were counted as osteoclasts and the number of pits formed on the dentine slices was determined to judge the activity of osteoclasts. Western blotting, RT-PCR and flow cytometer were used to detect the expression of OPG and RANKL in MC3T3-E1 cells. ResultsDiacerein significantly inhibited the formation and function of the cultured osteoclasts stimulated by IL-1β. sRANKL could reverse the effect of diacerein. Diacerein inhibited protein and mRNA expression of RANKL but enhanced those of OPG in MC3T3-E1 cells. ConclusionDiacerein may inhibit osteoclastic bone destruction through the inhibition of RANKL expression and the increase of OPG expression in MC3T3-E1 cells.