Exp Mol Med.  2006 Jun;38(3):256-264.

Tanshinone IIA inhibits osteoclast differentiation through down-regulation of c-Fos and NFATc1

• Kwak HB
• Yang D
• Ha H
• Lee JH
• Kim HN
• Woo ER
• Lee S
• Kim HH
• Lee ZH

Abstract

Bone is a dynamic tissue that is regulated by the activity of bone-resorbing osteoclasts and bone-forming osteoblasts. Excessive osteoclast formation causes diseases such as osteoporosis and rheumatoid arthritis. Natural substances may be useful as therapeutic drugs to prevent many diseases in humans because they avoid the many side effects of treatment with chemical compounds. Here we show that tanshinone IIA isolated from Salvia miltiorrhiza Bunge inhibits the receptor activator of NF-kappaB ligand (RANKL)-mediated osteoclast differentiation of osteoclast precursors. Tanshinone IIA suppressed the expression levels of c-Fos and NFATc1 induced by RANKL. However, retrovirus-mediated overexpression of c-Fos induced the expression of NFATc1 despite the presence of tanshinone IIA and reversed the inhibitory effect of tanshinone IIA on osteoclast differentiation. Also, the introduction of osteoclast precursors with the NFATc1 retrovirus led to osteoclast differentiation in the presence of tanshinone IIA. Our results suggest that tanshinone IIA may have a role as a therapeutic drug in the treatment of bone disease such as osteoporosis.

Keyword

osteoclasts; tanshinone; Salvia miltiorrhiza; drugs, Chinese herbal; osteoporosis; RANK ligand

MeSH Terms

Reverse Transcriptase Polymerase Chain Reaction
Receptor Activator of Nuclear Factor-kappa B
RANK Ligand
Proto-Oncogene Proteins c-fos/genetics/*metabolism
Phenanthrenes/*pharmacology
Osteoclasts/cytology/*drug effects/metabolism
NFATC Transcription Factors/genetics/*metabolism
Mice, Inbred ICR
Mice
Membrane Glycoproteins/genetics/metabolism/pharmacology
Male
Macrophage Colony-Stimulating Factor/pharmacology
Immunoblotting
Gene Expression/drug effects/genetics
Down-Regulation/drug effects
Cells, Cultured
Cell Differentiation/*drug effects
Carrier Proteins/genetics/metabolism/pharmacology
Bone Marrow Cells/cytology/drug effects/metabolism
Animals