Brunetti Giacomina, Oranger Angela, Mori Giorgio, Sardone Francesca, Pignataro Paolo, Coricciati Marco, Napoli Nicola, Rizzi Rita, Liso Vincenzo, Grassi Felice Roberto, Grano Maria, Colucci Silvia
Department of Human Anatomy and Histology, University of Bari, Bari, Italy.
Front Biosci (Elite Ed). 2011 Jun 1;3(3):1154-61. doi: 10.2741/e318.
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.
尽管破骨细胞（OCs）在RANK/RANKL/OPG系统的控制下分化，但许多炎性细胞因子可在与骨质流失相关的疾病中促进破骨细胞生成增加。最近，不同的研究表明TRAIL参与调节破骨细胞生成。在此，我们利用来自健康供体以及患有多发性骨髓瘤或牙周病患者的外周血单个核细胞（PBMCs）所代表的体外破骨细胞生成模型，研究了TRAIL在有骨受累的生理和病理条件下对破骨细胞形成的影响。我们证明，在来自健康供体的PBMCs中，TRAIL在无RANKL的情况下可直接诱导破骨细胞形成，而与RANKL同时添加时则发挥抑制作用。在来自患者的PBMCs中，TRAIL、RANKL和OPG水平升高，TRAIL的中和作用可部分抑制破骨细胞形成，而添加RANKL可逆转这种作用。最后，我们检测到患者血清中TRAIL水平较高。总之，我们的结果表明TRAIL在生理和病理条件下调节破骨细胞分化中可能发挥不同作用。
