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.
Miyamoto
Ichiko
I
Faculty of Agriculture, Kyushu University, 6-10-1 Hakozaki, Higashi-ku, Fukuoka, 812-8581, Japan.
Liu
Jie
J
Shimizu
Kuniyoshi
K
Sato
Masao
M
Kukita
Akiko
A
Kukita
Toshio
T
Kondo
Ryuichiro
R
D000818:Animals; D015519:Bone Density / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects*; D002459:Cell Fusion; D003713:Dendritic Cells / Q000187:drug effects / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D050778:NFATC Transcription Factors / Q000235:genetics / Q000378:metabolism; D010010:Osteoclasts / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D010012:Osteogenesis / Q000187:drug effects; D010052:Ovariectomy; D010936:Plant Extracts / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics / Q000378:metabolism; D053245:RANK Ligand / Q000037:antagonists & inhibitors; D051381:Rats; D017207:Rats, Sprague-Dawley; D020940:Reishi / Q000737:chemistry*; D014315:Triterpenes / Q000302:isolation & purification / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000494:pharmacology
D008565:Membrane Proteins; D050778:NFATC Transcription Factors; D010936:Plant Extracts; D016760:Proto-Oncogene Proteins c-fos; D053245:RANK Ligand; D014315:Triterpenes; D014409:Tumor Necrosis Factor-alpha; C528901:ganoderic acid D; C534033:ganoderic acid Me