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The death receptor DR5 is involved in TRAIL-mediated human osteoclast apoptosis

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Abstract

The number and activity of osteoclasts (OCs) are critical for maintaining normal bone turnover. The number is determined by the rates of cell differentiation and death. TNF-related apoptosis-inducing ligand (TRAIL), a member of the TNF superfamily, induces apoptosis by interacting with its death receptors, (DR4, DR5). However, its activity can be modulated by two decoy receptors, (DcR1 and DcR2). In this paper we show that TRAIL treatment causes reduced OC viability as well as an increased apoptotic OC number. Loss of nuclei integrity and derangement of the actin microfilament were also induced by TRAIL in OCs. Moreover, we demonstrated the expression of all TRAIL receptors in both precursors and differentiated OCs, and the upregulation of DR5 during OC differentiation. Interestingly, DcR2 was upregulated in the early stage of osteoclastogenesis and downregulated at the end of the differentiation process. We showed that DR5, upregulated by TRAIL, could be the mediator of TRAIL-induced OC apoptosis, since the addition of anti-DR5 neutralizing antibodies restores the OC viability previously reduced by TRAIL. Furthermore, the intracellular pathway induced by TRAIL in OCs involves caspase-8 and Bid activation. In conclusion, our data highlight an important role for the TRAIL/TRAIL receptor system in the regulation of OC apoptosis.

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Acknowledgement

We thank to Dr. Luigi Branca for expert technical support. This investigation was supported by Ministero dell’Istruzione Università e Ricerca (ex 60% grant to M. Grano) and by Agenzia Spaziale Italiana (ASI - OSMA grant to Maria Grano).

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Authors and Affiliations

  1. Department of Human Anatomy and Histology, University of Bari Medical School, Piazza Giulio Cesare, 11, Bari, 70124, Italy

    Silvia Colucci, Giacomina Brunetti, Angela Oranger, Paolo Pignataro, Roberto Tamma, Alberta Zallone & Maria Grano

  2. Clinica Reumatologica “M. Carrozzo”, University of Foggia, Foggia, Italy

    Francesco Paolo Cantatore

  3. Dipartimento di Scienze Biomediche, University of Foggia, Foggia, Italy

    Giorgio Mori

  4. Department of Oral Science, Section of Oral Surgery, University of Bari, Bari, Italy

    Felice Roberto Grassi

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  1. Silvia Colucci
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  2. Giacomina Brunetti
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  3. Francesco Paolo Cantatore
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  4. Angela Oranger
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  9. Alberta Zallone
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  10. Maria Grano
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Correspondence to Maria Grano.

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Colucci, S., Brunetti, G., Cantatore, F.P. et al. The death receptor DR5 is involved in TRAIL-mediated human osteoclast apoptosis. Apoptosis 12, 1623–1632 (2007). https://doi.org/10.1007/s10495-007-0095-3

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  • DOI: https://doi.org/10.1007/s10495-007-0095-3

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