Inhibition of osteoclast differentiation and bone resorption by tanshinone IIA isolated from Salvia miltiorrhiza Bunge

Hong Hee Kim, Jung Ha Kim, Han Bok Kwak, Hao Huang, Song Hee Han, Hyunil Ha, Soo Woong Lee, Eun Ran Woo, Zang Hee Lee*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

69 Scopus citations

Abstract

Osteoclasts, multinuclear cells specialized for bone resorption, differentiate from the monocyte/macrophage lineage of hematopoietic cells. Intervention in osteoclast differentiation is considered an effective therapeutic approach to the treatment of bone diseases involving osteoclasts. In this study, we found that tanshinone IIA, originating from Salvia miltiorrhiza Bunge, inhibited the differentiation of osteoclasts. Addition of tanshinone IIA to the osteoclast precursor culture caused a significant decrease in the level of calcitonin receptor, c-Src, and integrin β3 mRNA, which are normally upregulated during the osteoclast differentiation dependent on RANKL (receptor activator of nuclear factor kappa B ligand). RANKL activated the ERK, Akt, and NF-κB signal transduction pathways in osteoclast precursor cells, and tanshinone IIA suppressed this activation. Tanshinone IIA also inhibited the bone resorptive activity of differentiated osteoclasts, which was accompanied with the disruption of the actin ring. Thus, tanshinone IIA has the potential to ameliorate bone-resorption diseases in vivo by reducing both the number and activity of osteoclasts.

Original languageEnglish (US)
Pages (from-to)1647-1656
Number of pages10
JournalBiochemical Pharmacology
Volume67
Issue number9
DOIs
StatePublished - May 1 2004

Keywords

  • ERK
  • Extracellular signal-regulated kinase
  • M-CSF
  • Macrophage colony stimulating factor
  • NF-κB
  • Nuclear factor kappa B
  • Osteoclast
  • RANKL
  • Receptor activator of nuclear factor kappa B ligand
  • Tanshinone IIA
  • Tartrate-resistant acid phosphatase
  • TRAP

ASJC Scopus subject areas

  • Biochemistry
  • Pharmacology

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