Lenalidomide restores the osteogenic differentiation of bone marrow mesenchymal stem cells from multiple myeloma patients via deactivating Notch signaling pathway

Juan Guo; Chengming Fei; Youshan Zhao; Sida Zhao; Qingqing Zheng; Jiying Su; Dong Wu; Xiao Li; Chunkang Chang

doi:10.18632/oncotarget.19265

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Research Papers:

Lenalidomide restores the osteogenic differentiation of bone marrow mesenchymal stem cells from multiple myeloma patients via deactivating Notch signaling pathway

Juan Guo, Chengming Fei, Youshan Zhao, Sida Zhao, Qingqing Zheng, Jiying Su, Dong Wu, Xiao Li and Chunkang Chang _

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Oncotarget. 2017; 8:55405-55421. https://doi.org/10.18632/oncotarget.19265

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Abstract

Juan Guo1, Chengming Fei1, Youshan Zhao1, Sida Zhao1, Qingqing Zheng1, Jiying Su1, Dong Wu1, Xiao Li1 and Chunkang Chang1

1Department of Hematology, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai 200233, China

Correspondence to:

Chunkang Chang, email: [email protected]

Keywords: mesenchymal stem cells, multiple myeloma, osteogenic differentiation, Notch signaling, lenalidomide

Received: February 14, 2017 Accepted: June 24, 2017 Published: July 15, 2017

ABSTRACT

Multiple myeloma (MM) always presents osteolytic bone lesions, resulting from the abnormal osteoblastic and osteoclastic function in patients. MM patients exhibit the impairment of osteogenic differentiation of BMMSCs (bone marrow mesenchymal stem cells) and osteoblast deficiency. Effects of the drug, lenalidomide on the osteoblastic functions and the involved mechanisms remain unexplored. In the present study, it is observed that the osteogenic differentiation of BMMSCs from MM patients (MM-MSCs) is impaired and activation of Notch signaling pathway in MM-MSCs is abnormal. Notch signaling activation inhibits BMMSCs osteogenesis. Knockdown of Notch1 expression and DAPT application reverse the osteogenic differentiation from MM-MSCs. Furthermore, it is shown that the gene expression of Notch signaling molecules, including receptors, ligands and downstream factors are significantly decreased in MM-MSCs following lenalidomide treatment, compared with non-treated MM-MSCs. Taken together, treatment with lenalidomide restores the osteogenic differentiation of MM-MSCs via deactivating Notch signaling pathway.

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PII: 19265

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Research Papers:

Lenalidomide restores the osteogenic differentiation of bone marrow mesenchymal stem cells from multiple myeloma patients via deactivating Notch signaling pathway

Abstract