Tanshinone IIA inhibits osteoclast differentiation through down-regulation of c-Fos and NFATc1.
- Author:
Han Bok KWAK
1
;
Daum YANG
;
Hyunil HA
;
Jong Ho LEE
;
Ha Neui KIM
;
Eun Ran WOO
;
Seungbok LEE
;
Hong Hee KIM
;
Zang Hee LEE
Author Information
1. Department of Cell and Developmental Biology, School of Dentistry, DRI, and BK21 Program, Seoul National University, Seoul 110-749, Korea. zang1959@hotmail.com
- Publication Type:Original Article ; Research Support, Non-U.S. Gov't
- Keywords:
osteoclasts;
tanshinone;
Salvia miltiorrhiza;
drugs, Chinese herbal;
osteoporosis;
RANK ligand
- MeSH:
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
- From:Experimental & Molecular Medicine
2006;38(3):256-264
- CountryRepublic of Korea
- Language:English
-
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.
