[Frontiers in Bioscience E3, 1154-1161, June 1, 2011]

TRAIL effect on osteoclast formation in physiological and pathological conditions

Giacomina Brunetti1, Angela Oranger1, Giorgio Mori2, Francesca Sardone1, Paolo Pignataro1, Marco Coricciati1, Nicola Napoli3, Rita Rizzi4, Vincenzo Liso4, Felice Roberto Grassi5, Maria Grano1, Silvia Colucci1

1Department of Human Anatomy and Histology, University of Bari, Italy, 2Department of Biomedical Science, University of Foggia, Italy, 3Division of Endocrinology, Università Campus Bio-Medico, Rome, Italy, 4Hematology Section, Department of Pathology, University of Bari, Italy, 5Department of Oral Science, Section of Oral Surgery, University of Bari, Italy

TABLE OF CONTENTS

1. Abstract
2. Introduction
3. Materials and Methods
3.1. Patients
3.2. Cell cultures
3.3. ELISA assay
3.4. Statistical analyses
4. Results
4.1. TRAIL induces osteoclast differentiation in human PBMCs from healthy subjects
4.2. TRAIL neutralization inhibits the formation of osteoclasts from PBMCs of MM and Pd patients
4.3. High TRAIL levels in the media of PBMC cultures and in the sera from patients with periodontal disease and multiple myeloma
5. Discussion
6. Acknowledgment
7. References

1. ABSTRACT

Although osteoclasts (OCs) differentiate under the control of RANK/RANKL/OPG system, a number of inflammatory cytokines can contribute to increase osteoclastogenesis in diseases associated with bone loss. Recently, different studies indicate that TRAIL is implicated in modulating osteoclastogenesis. Here, we investigated the effect of TRAIL on OC formation in physiological and pathological conditions with bone involvement utilizing osteoclastogenesis in vitro models represented by peripheral blood mononuclear cells (PBMCs) from healthy donors and patients affected by multiple myeloma or periodontal disease. We demonstrated that in PBMCs from healthy donors TRAIL can directly induce OC formation in the absence of RANKL, while exert an inhibitory effect when added concomitantly to RANKL. In PBMCs from the patients, in which media the levels of TRAIL, RANKL and OPG are elevated, the neutralization of TRAIL partially inhibits the OC formation, and this effect was reversed by RANKL addition. Finally, we detect high TRAIL levels in the sera from the patients. In conclusion, our results indicate that TRAIL could exert a different role in modulating OC differentiation in physiological and pathological conditions.