Characterization of Wnt/beta-catenin signalling in osteoclasts in multiple myeloma.
Characterization of Wnt/beta-catenin signalling in osteoclasts in multiple myeloma.
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DOI：
10.1111/j.1365-2141.2009.08009.x
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发表时间：
2010-03
影响因子：
6.5
通讯作者：
Shaughnessy JD Jr
中科院分区：
文献类型：
--
作者：
Qiang YW;Chen Y;Brown N;Hu B;Epstein J;Barlogie B;Shaughnessy JD Jr
我们近期发现，在骨髓微环境或多发性骨髓瘤（MM）细胞中增强Wnt/β -连环蛋白信号传导，可明显抑制SCID - hu小鼠的破骨细胞生成；然而，这种对破骨细胞生成的调节可能直接源于破骨细胞中Wnt/β -连环蛋白信号传导的激活，也可能间接源于对成骨细胞的影响。本研究对Wnt/β -连环蛋白信号传导及其在破骨细胞中的潜在作用进行了特征分析。对WNT、FZD、LRP和TCF基因家族表达的系统分析表明，MM患者的人类破骨细胞中表达了众多Wnt信号传导成分。通过总β -连环蛋白和活性β -连环蛋白的积累以及在Wnt3a或LiCl作用下Dvl - 3蛋白的增加，确定了功能性Wnt/β -连环蛋白信号传导。此外，Wnt拮抗剂Dkk1和sFRP1可减弱Wnt诱导的β -连环蛋白和Dvl - 3的增加。最后，Wnt3a诱导的TCF/LEF转录活性表明经典Wnt信号传导在破骨细胞中是有活性的。与对照细胞的上清液相比，表达显性负性β -连环蛋白的成骨细胞克隆的上清液可显著刺激源自原发性MM的破骨细胞形成抗酒石酸酸性磷酸酶阳性的破骨细胞。这些结果表明，在MM中，Wnt/β -连环蛋白信号传导在破骨细胞中是有活性的，并且参与骨髓中的破骨细胞生成，在MM中它以一种依赖成骨细胞的方式作为破骨细胞形成的负调节因子。
We recently showed that increasing Wnt/β-catenin signalling in the bone marrow microenvironment or in multiple myeloma (MM) cells clearly suppresses osteoclastogenesis in SCID-hu mice; however, this regulation of osteoclastogenesis could result directly from activation of Wnt/β-catenin signalling in osteoclasts or indirectly from effects on osteoblasts. The present studies characterized Wnt/β-catenin signalling and its potential role in osteoclasts. Systematic analysis of expression of WNT, FZD, LRP and TCF gene families demonstrated that numerous Wnt-signalling components were expressed in human osteoclasts from patients with MM. Functional Wnt/β-catenin signalling was identified by accumulation of total and active β-catenin and increases in Dvl-3 protein in response to Wnt3a or LiCl. Furthermore, Wnt-induced increases in β-catenin and Dvl-3 were attenuated by Wnt antagonists Dkk1 and sFRP1. Finally, Wnt3a-induced TCF/LEF transcriptional activity suggests that canonical Wnt signalling is active in osteoclasts. Supernatants from dominant-negative-β-catenin–expressing osteoblast clones significantly stimulated tartrate-resistant acid phosphatase–positive osteoclast formation from primary MM-derived osteoclasts, compared with supernatants from control cells. These results suggested that Wnt/β-catenin signalling is active in osteoclasts in MM and is involved in osteoclastogenesis in bone marrow, where it acts as a negative regulator of osteoclast formation in an osteoblast-dependent manner in MM.
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影响因子：
20.3
作者：
Qiang, YW;Yao, L;Rudikoff, S
通讯作者：
Rudikoff, S
影响因子：
64.5
作者：
Gong, YQ;Slee, RB;Warman, ML
通讯作者：
Warman, ML
影响因子：
20.3
作者：
Qiang, YW;Kopantzev, E;Rudikoff, S
通讯作者：
Rudikoff, S
影响因子：
3.1
作者：
Qiang, YW;Rudikoff, S
通讯作者：
Rudikoff, S
影响因子：
4.8
作者：
Lee, JS;Ishimoto, A;Yanagawa, S
通讯作者：
Yanagawa, S