LAUSR

BACKGROUND/PURPOSE It remains unclear what role curcumin plays in the autophagy of osteoclast precursors (OCPs) during osteoclastogenesis, since some researchers found that curcumin has the ability to inhibit osteoclastogenesis. While others have considered it as an autophagy activator. This study aimed to determine the effect of curcumin-regulated autophagy on osteoclastogenesis. RESULTS The results revealed that direct administration of curcumin enhanced the OCP autophagy response in bone marrow-derived macrophages (BMMs). Curcumin could also abate RANKL's stimulatory effect on OCP autophagy and osteoclastogenesis. Autophagic suppression related to pharmacological inhibitors or gene silencing could further enhance the inhibitory effect of curcumin on osteoclastogenesis. As expected, curcumin ameliorated ovariectomy (OVX)-induced bone loss and its effect could be promoted by an autophagy inhibitor (chloroquine). CONCLUSIONS In conclusion, curcumin can directly enhance the autophagic activity of OCPs, which inhibits its anti-osteoclastogeneic effects. Autophagy inhibition-based drugs are expected to enhance curcumin's efficacy in treating osteoporosis.