A role for IL-34 in osteolytic disease of multiple myeloma
A role for IL-34 in osteolytic disease of multiple myeloma
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DOI：
10.1182/bloodadvances.2018020008
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发表时间：
2019-02-26
期刊：
影响因子：
7.5
通讯作者：
Seino, Ken-ichiro
中科院分区：
文献类型：
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作者：
Baghdadi, Muhammad;Ishikawa, Kozo;Seino, Ken-ichiro
多发性骨髓瘤（MM）是一种恶性血液病，生长在中轴骨骼的多个部位，并导致使人衰弱的溶骨性疾病。白细胞介素-34（IL-34）是新近发现的一种细胞因子，作为集落刺激因子-1（CSF-1）受体的配体，可替代CSF-1促进破骨细胞分化。在这项研究中，我们确定IL-34作为破骨细胞生成细胞因子，加速溶骨性疾病在MM。IL-34被发现在鼠M细胞系MOPC 315中表达。骨髓，IL-34的表达增强刺激与促炎细胞因子或骨髓（BM）基质细胞。MM细胞衍生的IL-34促进小鼠骨髓细胞体外破骨细胞形成。通过特异性小干扰RNA靶向IL 34在体外损害破骨细胞形成，并在体内减弱溶骨性疾病。在MM患者的骨髓穿刺液中，CD 138（+）人群中IL-34的表达水平在患者之间从高到弱到不存在不等。MM细胞来源的IL-34促进人CD 14（+）单核细胞破骨细胞的形成，而IL-34的中和抗体可减少破骨细胞的形成。总之，本研究首次描述了IL-34在MM细胞中的表达，表明其可增强骨质溶解，并表明IL-34可作为控制MM患者病理性破骨细胞生成的潜在治疗靶点。
Multiple myeloma (MM) is a hematological malignancy that grows in multiple sites of the axial skeleton and causes debilitating osteolytic disease. Interleukin-34 (IL-34) is a newly discovered cytokine that acts as a ligand of colony-stimulating factor-1 (CSF-1) receptor and can replace CSF-1 for osteoclast differentiation. In this study, we identify IL-34 as an osteoclastogenic cytokine that accelerates osteolytic disease in MM. IL-34 was found to be expressed in the murine Mcell line MOPC315. BM, and the expression of IL-34 was enhanced by stimulation with proinflammatory cytokines or by bone marrow (BM) stromal cells. MM-cell-derived IL-34 promoted osteoclast formation from mouse BM cells in vitro. Targeting Il34 by specific small interfering RNA impaired osteoclast formation in vitro and attenuated osteolytic disease in vivo. In BM aspirates from MM patients, the expression levels of IL-34 in CD138(+) populations vary among patients from high to weak to absent. MM cell-derived IL-34 promoted osteoclast formation from human CD14(+) monocytes, which was reduced by a neutralizing antibody against IL-34. Taken together, this study describes for the first time the expression of IL-34 in MM cells, indicating that it may enhance osteolysis and suggesting IL-34 as a potential therapeutic target to control pathological osteoclastogenesis in MM patients.