Ginsenoside Rh2 inhibits osteoclastogenesis through down-regulation of NF-κB, NFATc1 and c-Fos

Korea Research Institute of Bioscience and Biotechnology, Ochang, Cheongwon, South Korea.
Bone (Impact Factor: 3.97). 03/2012; 50(6):1207-13. DOI: 10.1016/j.bone.2012.03.022
Source: PubMed


Ginsenoside Rh2 is one of the most active components of red ginseng, controlling cancer and other metabolic diseases including osteoclast differentiation. However, the molecular mechanism underlying the inhibition of osteoclast differentiation by ginsenoside Rh2 remains poorly understood. In the present study, it was found that ginsenoside Rh2 suppressed osteoclast differentiation from bone marrow macrophages (BMMs) treated with receptor activator of nuclear factor κB ligand (RANKL) without any cytotoxicity. Ginsenoside Rh2 significantly reduced RANKL-induced expression of transcription factors, c-Fos and nuclear factor of activated T-cells (NFATc1), as well as osteoclast markers, TRAP and OSCAR. In defining the signaling pathways, ginsenoside Rh2 was shown to moderately inhibit NF-κB activation and ERK phosphorylation in response to RANKL stimulation in BMM cells without any effect on p38 and c-Jun N-terminal kinase (JNK). Finally, ginsenoside Rh2 blocked osteoporosis in vivo as confirmed by restored bone mineral density (BMD) and other markers associated osteoclast differentiation. Hence, it is suggested that ginsenoside Rh2 could suppress RANKL-induced osteoclast differentiation in vitro and in vivo through the regulation of c-Fos and NFATc1 expressions, not excluding the involvement of NF-κB and ERK. Ginsenoside Rh2 is also suggested to be developed as a therapeutic drug for prevention and treatment of osteoporosis.

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Available from: Byung-Chul Oh, Oct 03, 2015
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    • "In addition to NF-κB pathway, three well-known MAPKs (ERK, JNK, and p38) are also activated by RANKL stimulation and play important roles in osteoclast differentiation. Previous studies by our and other groups have demonstrated that the inhibition of ERK activation suppresses osteoclast formation (He et al., 2012; Kim et al., 2007; 2014a). In the present study, capric acid specifically blocked the phosphorylation of ERK by RANKL, whereas it did not affect the activation of JNK and p38. "
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    ABSTRACT: Fatty acids, important components of a normal diet, have been reported to play a role in bone metabolism. Osteoclasts are bone-resorbing cells that are responsible for many bone-destructive diseases such as osteoporosis. In this study, we investigated the impact of a medium-chain fatty acid, capric acid, on the osteoclast differentiation, function, and survival induced by receptor activator of NF-kappaB ligand (RANKL) and macrophage colony-stimulating factor (MCSF). Capric acid inhibited RANKL-mediated osteoclastogenesis in bone marrow-derived macrophages and suppressed RANKL-induced IkappaBalpha phosphorylation, p65 nuclear translocation, and NF-kappaB transcriptional activity. Capric acid further blocked the RANKL-stimulated activation of ERK without affecting JNK or p38. The induction of NFATc1 in response to RANKL was also attenuated by capric acid. In addition, capric acid abrogated M-CSF and RANKLmediated cytoskeleton reorganization, which is crucial for the efficient bone resorption of osteoclasts. Capric acid also increased apoptosis in mature osteoclasts through the induction of Bim expression and the suppression of ERK activation by M-CSF. Together, our results reveal that capric acid has inhibitory effects on osteoclast development. We therefore suggest that capric acid may have potential therapeutic implications for the treatment of bone resorption-associated disorders.
    Molecules and Cells 08/2014; 37(8). DOI:10.14348/molcells.2014.0153 · 2.09 Impact Factor
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    • "In CIA joints, the decrease in number of Th17 cells, seems to have resulted in a reduction in TRAP(+) osteoclasts. The inhibitory effect of RGE on osteoclastogenesis in vitro was previously reported by He et al. [33]. They demonstrated that ginsenoside Rh2, a component of red ginseng, suppressed osteoclast differentiation by inhibiting RANKL-induced c-fos and NFATc1 expression. "
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    • "Some studies verified that ginsenosides appear to inhibit the osteoclastic bone resorption via depression of the new osteoclast formation. These results obviously demonstrated that ginsenosides appear to be the effective component in the osteoclastgenesis inhibition, which has great potential in the treatment of osteoporosis and in bone metastases therapeutics with less side effects than other treatments [23-25]. In the present study, the effects of KRG extract on bone were evaluated. "
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