Caffeic acid phenethyl ester, an active component of honeybee propolis attenuates osteoclastogenesis and bone resorption via the suppression of RANKL-induced NF-κB and NFAT activity

Authors

  • Estabelle S.M. Ang,

    1. Molecular Orthopaedic Laboratory, Centre for Orthopaedic Research, School of Surgery, The University of Western Australia, Nedlands, Western Australia, Australia
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  • Nathan J. Pavlos,

    1. Molecular Orthopaedic Laboratory, Centre for Orthopaedic Research, School of Surgery, The University of Western Australia, Nedlands, Western Australia, Australia
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  • Lee Y. Chai,

    1. Molecular Orthopaedic Laboratory, Centre for Orthopaedic Research, School of Surgery, The University of Western Australia, Nedlands, Western Australia, Australia
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  • Ming Qi,

    1. Molecular Orthopaedic Laboratory, Centre for Orthopaedic Research, School of Surgery, The University of Western Australia, Nedlands, Western Australia, Australia
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  • Tak S. Cheng,

    1. Molecular Orthopaedic Laboratory, Centre for Orthopaedic Research, School of Surgery, The University of Western Australia, Nedlands, Western Australia, Australia
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  • James H. Steer,

    1. Pharmacology Unit, School of Medicine and Pharmacology, The University of Western Australia, Nedlands, Western Australia, Australia
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  • David A. Joyce,

    1. Pharmacology Unit, School of Medicine and Pharmacology, The University of Western Australia, Nedlands, Western Australia, Australia
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  • Ming H. Zheng,

    1. Molecular Orthopaedic Laboratory, Centre for Orthopaedic Research, School of Surgery, The University of Western Australia, Nedlands, Western Australia, Australia
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  • Jiake Xu

    Corresponding author
    1. Molecular Orthopaedic Laboratory, Centre for Orthopaedic Research, School of Surgery, The University of Western Australia, Nedlands, Western Australia, Australia
    • Molecular Orthopaedic Laboratory, Centre for Orthopaedic Research, School of Surgery, University of Western Australia, QEII Medical Centre, 2nd Floor M Block, Nedlands 6009, WA, Australia.
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Abstract

Receptor activator NF-κB ligand (RANKL)-activated signaling is essential for osteoclast differentiation, activation and survival. Caffeic acid phenethyl ester (CAPE), a natural NF-κB inhibitor from honeybee propolis has been shown to have anti-tumor and anti-inflammatory properties. In this study, we investigated the effect of CAPE on the regulation of RANKL-induced osteoclastogenesis, bone resorption and signaling pathways. Low concentrations of CAPE (<1 µM) dose dependently inhibited RANKL-induced osteoclastogenesis in RAW264.7 cell and bone marrow macrophage (BMM) cultures, as well as decreasing the capacity of human osteoclasts to resorb bone. CAPE inhibited both constitutive and RANKL-induced NF-κB and NFAT activation, concomitant with delayed IκBα degradation and inhibition of p65 nuclear translocation. At higher concentrations, CAPE induced apoptosis and caspase 3 activities of RAW264.7 and disrupts the microtubule network in osteoclast like (OCL) cells. Taken together, our findings demonstrate that inhibition of NF-κB and NFAT activation by CAPE results in the attenuation of osteoclastogenesis and bone resorption, implying that CAPE is a potential treatment for osteolytic bone diseases. J. Cell. Physiol. 221: 642–649, 2009. © 2009 Wiley-Liss, Inc.

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