骨保护素/肿瘤坏死因子相关凋亡诱导配体复合物在多发性骨髓瘤中的作用：源自人多发性骨髓瘤骨病的体外破骨细胞生成模型中的骨保护素/肿瘤坏死因子相关凋亡诱导配体复合物

The role of OPG/TRAIL complex in multiple myeloma: the OPG/TRAIL complex in an in vitro osteoclastogenesis model derived from human multiple myeloma-bone disease.

作者信息

Brunetti Giacomina, Colucci Silvia, Rizzi Rita, Mori Giorgio, Colaianni Graziana, Oranger Angela, Zallone Alberta, Liso Vincenzo, Grano Maria

机构信息

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

出版信息

Ann N Y Acad Sci. 2006 Apr;1068:334-40. doi: 10.1196/annals.1346.049.

DOI:10.1196/annals.1346.049

PMID:16831934

Abstract

Multiple myeloma (MM) is often associated with an increased osteoclast (OC) activity. Using an in vitro osteoclastogenesis model consisting of MM unstimulated and unfractionated peripheral blood mononuclear cells (PBMCs), we showed that T cells support OC formation and survival. Differently, in T cell-depleted MM PBMC cultures, exogenous macrophage-colony stimulating factor (M-CSF) and receptor activated of nuclear factor-kappaB ligand (RANKL) were necessary for osteoclastogenesis. We found RANKL, OPG, and TRAIL overexpression by fresh MM T cells. Despite high osteoprotegerin (OPG) levels, the persistence of osteoclastogenesis can be related to the formation of the OPG/TRAIL complex. Our results highlight that MM T cells support OC formation and survival, possibly involving OPG/TRAIL interaction.

摘要

多发性骨髓瘤（MM）常与破骨细胞（OC）活性增加相关。利用由未受刺激且未分离的多发性骨髓瘤外周血单个核细胞（PBMC）组成的体外破骨细胞生成模型，我们发现T细胞支持破骨细胞的形成和存活。不同的是，在去除T细胞的多发性骨髓瘤PBMC培养物中，外源性巨噬细胞集落刺激因子（M-CSF）和核因子κB受体活化因子配体（RANKL）是破骨细胞生成所必需的。我们发现新鲜的多发性骨髓瘤T细胞中RANKL、骨保护素（OPG）和肿瘤坏死因子相关凋亡诱导配体（TRAIL）过表达。尽管骨保护素（OPG）水平较高，但破骨细胞生成的持续存在可能与OPG/TRAIL复合物的形成有关。我们的结果表明，多发性骨髓瘤T细胞支持破骨细胞的形成和存活，可能涉及OPG/TRAIL相互作用。