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

Publisher: Elsevier Science Country of Publication: United States NLM ID: 8504048 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1873-2763 (Electronic) Linking ISSN: 18732763 NLM ISO Abbreviation: Bone Subsets: MEDLINE

Publication: New York : Elsevier Science
Original Publication: Elmsford, NY : Pergamon Press, c1985-

Ginsenosides/*pharmacology ; NF-kappa B/*metabolism ; NFATC Transcription Factors/*metabolism ; Osteoclasts/*drug effects ; Osteoclasts/*metabolism ; Proto-Oncogene Proteins c-fos/*metabolism; Animals ; Base Sequence ; Bone Resorption/genetics ; Bone Resorption/metabolism ; Bone Resorption/pathology ; Bone Resorption/prevention & control ; Cell Differentiation/drug effects ; Cells, Cultured ; DNA Primers/genetics ; Down-Regulation/drug effects ; Genes, fos ; MAP Kinase Signaling System/drug effects ; Macrophages/cytology ; Macrophages/drug effects ; Macrophages/metabolism ; Mice ; NFATC Transcription Factors/genetics ; Osteoclasts/cytology ; Osteoporosis/genetics ; Osteoporosis/metabolism ; Osteoporosis/pathology ; Osteoporosis/prevention & control ; Phosphorylation ; RANK Ligand/pharmacology

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.
(Copyright © 2012 Elsevier Inc. All rights reserved.)

0 (DNA Primers)
0 (Ginsenosides)
0 (NF-kappa B)
0 (NFATC Transcription Factors)
0 (Nfatc1 protein, mouse)
0 (Proto-Oncogene Proteins c-fos)
0 (RANK Ligand)
0 (Tnfsf11 protein, mouse)
78214-33-2 (ginsenoside Rh2)

Date Created: 20120410 Date Completed: 20120913 Latest Revision: 20120515

20221213

10.1016/j.bone.2012.03.022

22484180