Brain-derived neurotrophic factor is a potential osteoclast stimulating factor in multiple myeloma
Brain-derived neurotrophic factor is a potential osteoclast stimulating factor in multiple myeloma
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DOI：
10.1002/ijc.26059
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发表时间：
2012-02-15
影响因子：
6.4
通讯作者：
Hu, Yu
中科院分区：
文献类型：
--
作者：
Sun, Chun-Yan;Chu, Zhang-Bo;Hu, Yu
多发性骨髓瘤（MM）的特点是骨髓中单克隆浆细胞的积累和溶解性骨病变的进展。骨髓瘤患者骨吸收增强的机制尚未完全确定。我们之前已经确定了脑源性神经营养因子（BDNF）在MM细胞增殖和迁移中的作用。在我们的研究中，我们研究了BDNF是否可能参与MM细胞诱导的骨溶解。我们发现BDNF在MM患者中升高，骨髓血浆BDNF水平与骨病程度呈正相关。在破骨细胞形成实验中，MM患者的骨髓血浆增加了破骨细胞的形成，并且这种作用被BDNF中和抗体显著阻断，提示BDNF在破骨细胞活化中起关键作用。此外，重组BDNF对破骨细胞形成和骨吸收的直接作用支持了BDNF在MM骨病中的潜在作用。BDNF受体TrkB在人破骨细胞前体中表达，Trk抑制剂K252a显著抑制BDNF刺激的破骨细胞形成，表明BDNF利用TrkB对破骨细胞产生作用。最后，骨髓血浆BDNF水平与巨噬细胞炎症蛋白-1a和核因子受体激活因子-？这些结果支持BDNF在骨髓瘤骨病发展中的重要作用。
Multiple myeloma (MM) is characterized by accumulation of monoclonal plasma cells in the bone marrow and progression of lytic bone lesions. The mechanisms of enhanced bone resorption in patients with myeloma are not fully defined. We have previously identified the role of brain-derived neurotrophic factor (BDNF) in proliferation and migration of MM cells. In our study, we investigated whether BDNF was possibly involved in MM cell-induced osteolysis. We showed that BDNF was elevated in MM patients and the bone marrow plasma levels of BDNF positively correlated with extent of bone disease. In osteoclast formation assay, bone marrow plasma from patients with MM increased osteoclast formation and the effect was significantly blocked by neutralizing antibody to BDNF, suggesting a critical role for BDNF in osteoclast activation. Furthermore, the direct effects of recombinant BDNF on osteoclast formation and bone resorption support the potential role of BDNF in the MM bone disease. BDNF receptor TrkB was expressed by human osteoclast precursors and a Trk inhibitor K252a markedly inhibited osteoclast formation stimulated with BDNF, demonstrating that BDNF used TrkB for its effects on osteoclast. Finally, bone marrow plasma BDNF level positively correlated with macrophage inflammatory protein-1a and receptor activator of nuclear factor-?B ligand, two major osteoclast stimulatory factors in MM. These results support an important role for BDNF in the development of myeloma bone disease.