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
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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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