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-KB ligand (RANKL) and a tumor necrosis factor at (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 cl (NFATc1). This suppression leads to the inhibition of dendritic cell-specific transmembrane protein (DC-STAMP) expression and reduces osteoclast fusion. (C) 2008 Published by Elsevier B.V.