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Lenalidomide Restores the Osteogenic Differentiation of Bone Marrow Mesenchymal Stem Cells from Multiple Myeloma Patients Via Deactivating Notch Signaling Pathway

Overview
Journal Oncotarget
Specialty Oncology
Date 2017 Sep 15
PMID 28903429
Citations 12
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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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References
1.
Breitkreutz I, Raab M, Vallet S, Hideshima T, Raje N, Mitsiades C . Lenalidomide inhibits osteoclastogenesis, survival factors and bone-remodeling markers in multiple myeloma. Leukemia. 2008; 22(10):1925-32. DOI: 10.1038/leu.2008.174. View

2.
Arnulf B, Lecourt S, Soulier J, Ternaux B, Lacassagne M, Crinquette A . Phenotypic and functional characterization of bone marrow mesenchymal stem cells derived from patients with multiple myeloma. Leukemia. 2006; 21(1):158-63. DOI: 10.1038/sj.leu.2404466. View

3.
. Criteria for the classification of monoclonal gammopathies, multiple myeloma and related disorders: a report of the International Myeloma Working Group. Br J Haematol. 2003; 121(5):749-57. View

4.
Munemasa S, Sakai A, Kuroda Y, Okikawa Y, Katayama Y, Asaoku H . Osteoprogenitor differentiation is not affected by immunomodulatory thalidomide analogs but is promoted by low bortezomib concentration, while both agents suppress osteoclast differentiation. Int J Oncol. 2008; 33(1):129-36. View

5.
Zhao Y, Wu D, Fei C, Guo J, Gu S, Zhu Y . Down-regulation of Dicer1 promotes cellular senescence and decreases the differentiation and stem cell-supporting capacities of mesenchymal stromal cells in patients with myelodysplastic syndrome. Haematologica. 2014; 100(2):194-204. PMC: 4803146. DOI: 10.3324/haematol.2014.109769. View