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Curcumin diminishes human osteoclastogenesis by inhibition of the signalosome-associated IκB kinase

  • Ivana von Metzler
  • Holger Krebbel
  • Ulrike Kuckelkorn
  • Ulrike Heider
  • Christian Jakob
  • Martin Kaiser
  • Claudia Fleissner
  • Evangelos Terpos
  • Orhan Sezer
Original Paper

Abstract

Purpose

Curcumin is a natural polyphenolic derogate extracted from spice turmeric, exhibiting anti-inflammatory and chemopreventive activities. It was described to interact with the signalosome-associated kinases and the proteasome-ubiquitin system, which both are involved in the osteoclastogenesis. Thus, we hypothesized that curcumin could diminish osteoclast differentiation and function.

Methods

For the experiments considering osteoclast differentiation and resorptional activities, preosteoclasts were cultured for 4 weeks and treated with curcumin at subapoptotic dosages. Derived mature osteoclasts were identified as large, multinucleated cells with expression of tartrate-resistant acid phosphatase activity. Formation of resorption lacunae, a hallmark of osteoclast activity, was quantified using dentine pits and light microscopy. The signaling pathways were examined by ELISA-based methods and by immunoblotting.

Results

Both 1 and 10 μM curcumin abrogated osteoclast differentiation (by 56 and 81%) and function (by 56 and 99%) (P < 0.05) dose-dependently. The effects were accompanied by the inhibition of IκB phosphorylation and NF-κB activation. In contrast, subtoxic doses did not have any significant effects on proteasome inhibition.

Conclusion

This manuscript is the first report that describes the effects of curcumin toward human osteoclastogenesis, and builds the framework for clinical trials of curcumin in the treatment of cancer-induced lytic bone disease.

Keywords

Proteasome Curcumin NF-κB IκB Osteoclast Cancer 

Notes

Acknowledgments

This study was supported by the Deutsche Forschungsgemeinschaft (DFG Klinische Forschergruppe KFO 105).

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Copyright information

© Springer-Verlag 2008

Authors and Affiliations

  • Ivana von Metzler
    • 1
  • Holger Krebbel
    • 1
  • Ulrike Kuckelkorn
    • 2
  • Ulrike Heider
    • 1
  • Christian Jakob
    • 1
  • Martin Kaiser
    • 1
  • Claudia Fleissner
    • 1
  • Evangelos Terpos
    • 3
  • Orhan Sezer
    • 1
  1. 1.Department of Hematology and Oncology, Charitéplatz 1Charité, Universitätsmedizin BerlinBerlinGermany
  2. 2.Department of Biochemistry, Monbijoustrasse 2Charité, Universitätsmedizin BerlinBerlinGermany
  3. 3.Department of Hematology and Medical Research251 General Air Force HospitalAthensGreece

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