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

Abstract

Bone is a dynamic tissue that is regulated by the activity of bone-resorbing osteoclasts and boneforming osteoblasts. Excessive osteoclast forma - tion 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-κB ligand (RANKL)-mediated osteoclast differen - tiation of osteoclast precursors. Tanshinone IIA suppressed the expression levels of c-Fos and NFATc1 induced by RANKL. However, retrovirusmediated overexpression of c-Fos induced the expression of NFATc1 despite the presence of tans - hinone 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.