Ganoderma neo-japonicum extracts inhibit RANKL-induced osteoclastogenesis in RAW 264.7 murine macrophages

• Main Authors: Chin-huei Lee, 李晉卉
• Other Authors: Chi-Liang Chern
• Format: Others
• Language: zh-TW
• Published: 2018
• Online Access: http://ndltd.ncl.edu.tw/handle/9d35uj

碩士 === 國立中山大學 === 生物科學系研究所 === 106 === Although several current therapeutic drugs for postmenopausal osteoporosis are available, there is a need for alternatives with minimal side effects. The aim of this study was to evaluate the effects of water extract of Ganoderma neo-japonicum (GNES) on RANKL- induced osteoclast differentiation and investigated the underlying molecular mechanism(s) of action. GNES not only inhibited osteoclast formation of RAW 264.7 mouse macrophages, but also inhibited resorption pit formation in a dose-dependent manner. Mechanistically, GNES increased heme oxygenase-1 (HO-1) expression, and attenuated intracellular ROS production and nuclear translocation of nuclear factor of activated T-cells NFATc1, the master transcription regulator of osteoclast differentiation. Inhibition of HO-1 expression with HO-1 siRNA could reverse the inhibitory effect of GNES on osteoclast differentiation, ROS production and nuclear translocation of NFATc1, suggesting that HO-1 contributed to the attenuation of NFATc1-mediated osteoclastogenesis by GNES. In regarding to the signaling pathways regulating HO-1 expression, we found that GNES could induce Akt1 phosphorylation at Ser473, coincidentally with nuclear translocation of Nrf2 and enhancement of antioxidant response element (ARE)- driven luciferase activity. These results indicated the inhibitory effect of GNES on osteoclast differentiation is due to the decrease of ROS production, via the enhancement of Akt-Nrf2-HO-1 pathway, which ultimately suppresses NFATc1 translocation to nucleus.