IL-3 is a potential inhibitor of osteoblast differentiation in multiple myeloma
IL-3 is a potential inhibitor of osteoblast differentiation in multiple myeloma
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DOI：
10.1182/blood-2005-03-1080
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发表时间：
2005-08-15
期刊：
影响因子：
20.3
通讯作者：
Giuliani, N
中科院分区：
文献类型：
--
作者：
Ehrlich, LA;Chung, HY;Giuliani, N
多发性骨髓瘤的骨破坏的特征是明显增加了破骨骨骨破坏和严重受损的成骨细胞活性。我们报道说，与健康对照组相比，骨髓瘤患者的骨髓血浆中白细胞介素3（IL-3）水平升高，并且IL-3刺激破骨细胞的形成。但是，IL-3对成骨细胞的影响尚不清楚。因此，为了确定IL-3是否抑制成骨细胞的生长和分化，我们用IL-3处理了原代小鼠和人摩洛的基质细胞并评估成骨细胞分化。 IL-3以剂量依赖性方式抑制基底和骨形态学蛋白2（BMP-2）刺激的成骨细胞形成，而不会影响细胞生长。重要的是，来自高IL-3水平的患者的骨髓血浆抑制了成骨细胞分化，这可能会被抗IL-3阻断。但是，IL-3没有抑制成骨细胞样细胞系的成骨细胞分化。相反，IL-3增加了基质细胞培养物中CD45（+）造血细胞的数量。 CD45+细胞的耗竭消除了IL-3对成骨细胞的抑制作用，并重新建立了CD45+细胞的培养物恢复了IL-3抑制成骨细胞分化的能力。这些数据表明，IL-3通过刺激破骨细胞和间接抑制成骨细胞的形成，在骨髓瘤的骨骼破坏过程中起双重作用。
Bone destruction in multiple myeloma is characterized both by markedly increased osteoclastic bone destruction and severely impaired osteoblast activity. We reported that interleukin-3 (IL-3) levels are increased in bone marrow plasma of myeloma patients compared with healthy controls and that IL-3 stimulates osteoclast formation. However, the effects of IL-3 on osteoblasts are unknown. Therefore, to determine if IL-3 inhibits osteoblast growth and differentiation, we treated primary mouse and human mar-row stromal cells with IL-3 and assessed osteoblast differentiation. IL-3 inhibited basal and bone morphogenic protein-2 (BMP-2)-stimulated osteoblast formation in a dose-dependent manner without affecting cell growth. Importantly, marrow plasma from patients with high IL-3 levels inhibited osteoblast differentiation, which could be blocked by anti-IL-3. However, IL-3 did not inhibit osteoblast differentiation of osteoblastlike cell lines. In contrast, IL-3 increased the number of CD45(+) hematopoietic cells in stromal-cell cultures. Depletion of the CD45+ cells abolished the inhibitory effects of IL-3 on osteoblasts, and reconstitution of the cultures with CD45+ cells restored the capacity of IL-3 to inhibit osteoblast differentiation. These data suggest that IL-3 plays a dual role in the bone destructive process in myeloma by both stimulating osteoclasts and indirectly inhibiting osteoblast formation.