Regulation of osteoclastogenesis by ganoderic acid DM isolated from Ganoderma lucidum

The preventative effects of the ethanol extracts of Ganoderma lucidum against the ovariectomized (Ovx)-induced deterioration of bone density in 11-week-old female Sprague Dawley (SD) rats were investigated. The results showed that the G. lucidum-treated Ovx rats showed improved bone density compared with the Ovx rats. We studied the effects of G. lucidum on osteoclastic differentiation using bone marrow cells and RAW 264 cell D-clone (RAW-D). Differentiation, in response to receptor activator of NF-kappaB ligand (RANKL) and a tumor necrosis factor alpha (TNF-alpha), was inhibited by the ethanol extracts of G. lucidum and ganoderic acid DM which was isolated as one of the active compounds by bioassay-guided fractionation. Ganoderic acid DM especially suppresses the expression of c-Fos and nuclear factor of activated T cells c1 (NFATc1). This suppression leads to the inhibition of dendritic cell-specific transmembrane protein (DC-STAMP) expression and reduces osteoclast fusion.