Macrophage inflammatory protein-1α is an osteoclastogenic factor in myeloma that is independent of receptor activator of nuclear factor κB ligand
Macrophage inflammatory protein-1α is an osteoclastogenic factor in myeloma that is independent of receptor activator of nuclear factor κB ligand
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DOI：
10.1182/blood.v97.11.3349
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发表时间：
2001-06-01
期刊：
影响因子：
20.3
通讯作者：
Roodman, GD
中科院分区：
文献类型：
--
作者：
Han, JH;Choi, SJ;Roodman, GD
最近筛选了来自骨髓瘤患者骨髓样品的互补DNA表达文库，并鉴定出人巨噬细胞炎性蛋白-1 α（hMIP-1 α）为在这些样品中表达的破骨细胞生成因子。hMIP-1 α以剂量依赖性方式（5-200 pg/mL）促进人骨髓培养物中破骨细胞（OCL）的形成，并促进高度纯化的OCL前体的形成。此外，hMIP-1 α促进由人白细胞介素-6（IL-6）诱导的OCL的形成，所述人白细胞介素-6由骨髓基质细胞与骨髓瘤细胞相互作用时产生。hMIP-1 α还增强了由甲状旁腺相关蛋白（PTHrP）和核因子KB配体受体激活剂（RANKL）诱导的OCL形成，这些因子也与骨髓瘤骨病有关。时程研究显示，hMIP-1 α在3周培养期的最后2周起作用。逆转录-聚合酶链反应分析表明，hMIP-1 α（CCR 1和CCR 5）的趋化因子受体表达的人骨髓和高度纯化的早期OCL前体。此外，hMIP-1 α没有增加RANKL的表达。这些数据表明，hMIP-1 α是一种破骨细胞生成因子，似乎直接作用于人OCL祖细胞，并在OCL分化的后期阶段起作用。这些数据进一步表明，在患有骨髓瘤的患者中，由骨髓瘤细胞产生的MIP-1 α与由骨髓产生的RANKL和IL-6组合;响应于骨髓瘤细胞的基质细胞通过其对Od前体的组合作用增强OCL形成。（血。2001; 97：3349-3353）。
A complementary DNA expression library derived from marrow samples from myeloma patients was recently screened and human macrophage inflammatory protein-1 alpha (hMIP-1 alpha) was identified as an osteoclastogenic factor expressed in these samples. hMIP-1 alpha enhanced osteoclast (OCL) formation in human marrow cultures and by highly purified OCL precursors in a dose-dependent manner (5-200 pg/mL), Furthermore, hMIP-1 alpha enhanced OCL formation induced by human interleukin-6 (IL-6), which is produced by marrow stromal cells when they interact with myeloma cells. hMIP-1 alpha also enhanced OCL formation induced by parathyroid hormone-related protein (PTHrP) and receptor activator of nuclear factor KB ligand (RANKL), factors also implicated in myeloma bone disease. Time-course studies revealed that the hMIP-1 alpha acted during the last 2 weeks of the 3-week culture period. Reverse transcription-polymerase chain reaction analysis showed that the chemokine receptors for hMIP-1 alpha (CCR1 and CCR5) were expressed by human bone marrow and highly purified early OCL precursors. Furthermore, hMIP-1 alpha did not increase expression of RANKL, These data demonstrate that hMIP-1 alpha is an osteoclastogenic factor that appears to act directly on human OCL progenitors and acts at the later stages of OCL differentiation. These data further suggest that in patients with myeloma, MIP-la produced by myeloma cells, in combination with RANKL and IL-6 that are produced by marrow; stromal cells in response to myeloma cells, enhances OCL formation through their combined effects on Od precursors. (Blood. 2001; 97:3349-3353).