Cordyceps militaris mushroom and cordycepin inhibit RANKL-induced osteoclast differentiation.

Cordyceps militaris is a medicinal mushroom and its bioactive compound, cordycepin, is reported to have many pharmacological activities. The goal of this study was to investigate the effects of C. militaris extract (CME) and cordycepin on osteoclast differentiation in vitro and on an inflammatory bone loss in vivo. In RAW 264.7 cells, CME and cordycepin showed dose-dependent inhibition of receptor activator of the nuclear factor kappa B (NF-κB) ligand (RANKL)-induced osteoclast differentiation by TRAP (tartrate-resistant acid phosphatase) staining. Moreover, the mRNA expression of osteoclastogenesis-related genes (TRAP, cathepsin K, MMP-9, and NFATc1) was also inhibited by CME and cordycepin. Also, cordycepin significantly inhibited RANKL-induced phosphorylation of p38 and NF-κB, but not that of other members of mitogen-activated protein kinase families. To examine the effect of CME on bone loss in vivo, we used a mouse model of lipopolysaccharide (LPS)-mediated bone loss. Micro-CT analysis of the femurs showed that LPS treatment caused bone loss. However, bone loss was significantly attenuated in mice treated with CME. These results suggest that cordycepin or/and CME have inhibitory effects on osteoclast differentiation in vitro and that they suppress inflammatory bone loss in vivo.