Sclerostin is overexpressed by plasma cells from multiple myeloma patients
Sclerostin is overexpressed by plasma cells from multiple myeloma patients
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DOI：
10.1111/j.1749-6632.2011.06196.x
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发表时间：
2011-01-01
期刊：
影响因子：
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通讯作者：
Colucci, Silvia
中科院分区：
文献类型：
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作者：
Brunetti, Giacomina;Oranger, Angela;Colucci, Silvia
Sclerostin是骨细胞表达的骨形成负调节因子，是Wnt信号的抑制剂之一，Wnt信号是成骨细胞正确分化过程的关键途径。研究表明，Wnt信号通过Wnt抑制剂（如DKK1、sFRP-2和sFRP-3）的分泌，在多发性骨髓瘤（MM）骨病相关的成骨细胞活性降低中起关键作用。我们提供的证据表明，骨髓瘤细胞是人类骨髓瘤细胞系和浆细胞（CD138（+）细胞），从大量骨病MM患者的骨髓（BM）中获得。此外，我们发现MM患者和对照组之间的血清硬化蛋白水平没有差异。因此，我们的数据表明，MM细胞作为骨髓中的硬化蛋白来源，可以创造一个具有高硬化蛋白浓度的微环境，从而有助于抑制成骨细胞的分化。
Sclerostin, an osteocyte-expressed negative regulator of bone formation, is one of the inhibitors of Wnt signaling that is a critical pathway in the correct process of osteoblast differentiation. It has been demonstrated that Wnt signaling through the secretion of Wnt inhibitors, such as DKK1, sFRP-2, and sFRP-3, plays a key role in the decreased osteoblast activity associated with multiple myeloma (MM) bone disease. We provide evidence that sclerostin is expressed by myeloma cells that are human myeloma cell lines and plasma cells (CD138(+) cells) obtained from the bone marrow (BM) of a large number of MM patients with bone disease. Moreover, we show that there are no differences in sclerostin serum levels between MM patients and controls. Thus, our data indicate that MM cells, as a sclerostin source in the BM, could create a microenvironment with high sclerostin concentration that could contribute toward inhibiting osteoblast differentiation.