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This study evaluated as to whether curcumin (CCM) could ameliorate alveolar bone destruction in vivo and dissect its mechanism in vitro. The tartrate-resistant acid phosphatase (TRAP) activity, TRAP staining, quantitative RT-PCR, gelatin zymography, actin-ring formation, and pits formation assay were used to analyse the effect of CCM on receptor activator of nuclear factor κB ligand (RANKL)-induced osteoclast differentiation, activation, and function. Porphyromonas gingivalis LPS- and ligature-induced experimental periodontitis were established to evaluate the therapeutic benefits of CCM in vivo. The results demonstrated that CCM dose dependently diminishes RANKL-induced osteoclast differentiation, and osteoclastic specific genes expression accompanied by a significant attenuation of actin-ring and resorptive pits formation in vitro. Moreover, CCM reduces alveolar bone destruction, decreases TRAP-positive and polymorphonuclear cells infiltration, and suppresses myeloperoxidase activity in vivo. Thus, CCM reduces inflammatory bone loss in vivo by modulating RANKL-mediated osteoclast differentiation, activation, and function.