Upregulation of miR-135b Is Involved in the Impaired Osteogenic Differentiation of Mesenchymal Stem Cells Derived from Multiple Myeloma Patients

被引:68
|
作者
Xu, Song [1 ,2 ,3 ]
Santini, Gaia Cecilia [2 ]
De Veirman, Kim [2 ,3 ]
Vande Broek, Isabelle [3 ]
Leleu, Xavier [4 ]
De Becker, Ann [2 ]
Van Camp, Ben [3 ]
Vanderkerken, Karin [3 ]
Van Riet, Ivan [2 ,3 ]
机构
[1] Tianjin Med Univ, Gen Hosp, Lung Canc Inst, Dept Lung Canc Surg, Tianjin, Peoples R China
[2] Univ Ziekenhuis Brussel UZ Brussel, Div Clin Hematol, Stem Cell Lab, Brussels, Belgium
[3] Vrije Univ Brussel, Myeloma Ctr Brussels, Dept Hematol & Immunol, Brussels, Belgium
[4] CHU Lille, Serv Hematol, F-59037 Lille, France
来源
PLOS ONE | 2013年 / 8卷 / 11期
关键词
EXPRESSION; MICRORNAS; LINEAGE; MIRNA; PROLIFERATION; PROGRAM; PATHWAY; PROFILE; PCR; RNA;
D O I
10.1371/journal.pone.0079752
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Previous studies have demonstrated that mesenchymal stem cells from multiple myeloma (MM) patients (MM-hMSCs) display a distinctive gene expression profile, an enhanced production of cytokines and an impaired osteogenic differentiation ability compared to normal donors (ND-hMSCs). However, the underlying molecular mechanisms are unclear. In the present study, we observed that MM-hMSCs exhibited an abnormal upregulation of miR-135b, showing meanwhile an impaired osteogenic differentiation and a decrease of SMAD5 expression, which is the target of miR-135b involved in osteogenesis. By gain and loss of function studies we confirmed that miR-135b negatively regulated hMSCs osteogenesis. We also found that MM cell-produced factors stimulated ND-hMSCs to upregulate the expression of miR-135b. Importantly, treatment with a miR-135b inhibitor promoted osteogenic differentiation in MM-hMSCs. Finally, we observed that MM cell-derived soluble factors could induce an upregulation of miR-135b expression in ND-hMSCs in an indirect coculture system and the miR-135b expression turned to normal level after the removal of MM cells. Collectively, we provide evidence that miR-135b is involved in the impaired osteogenic differentiation of MSCs derived from MM patients and might therefore be a promising target for controlling bone disease.
引用
收藏
页数:11
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