Extracellular Vesicle microRNAs Contribute to the Osteogenic Inhibition of Mesenchymal Stem Cells in Multiple Myeloma
Open Access
- 13 February 2020
- Vol. 12 (2), 449
- https://doi.org/10.3390/cancers12020449
Abstract
Osteolytic bone disease is the major complication associated with the progression of multiple myeloma (MM). Recently, extracellular vesicles (EVs) have emerged as mediators of MM-associated bone disease by inhibiting the osteogenic differentiation of human mesenchymal stem cells (hMSCs). Here, we investigated a correlation between the EV-mediated osteogenic inhibition and MM vesicle content, focusing on miRNAs. By the use of a MicroRNA Card, we identified a pool of miRNAs, highly expressed in EVs, from MM cell line (MM1.S EVs), expression of which was confirmed in EVs from bone marrow (BM) plasma of patients affected by smoldering myeloma (SMM) and MM. Notably,we found that miR-129-5p, which targets different osteoblast (OBs) differentiation markers, is enriched in MM-EVs compared to SMM-EVs, thus suggesting a selective packaging correlated with pathological grade. We found that miR-129-5p can be transported to hMSCs by MM-EVs and, by the use of miRNA mimics, we investigated its role in recipient cells. Our data demonstrated that the increase of miR-129-5p levels in hMSCs under osteoblastic differentiation stimuli inhibited the expression of the transcription factor Sp1, previously described as a positive modulator of osteoblastic differentiation, and of its target the Alkaline phosphatase (ALPL), thus identifying miR-129-5p among the players of vesicle-mediated bone disease.Funding Information
- Associazione Italiana per la Ricerca sul Cancro (18783)
This publication has 80 references indexed in Scilit:
- Multiple myeloma-derived exosomes are enriched of amphiregulin (AREG) and activate the epidermal growth factor pathway in the bone microenvironment leading to osteoclastogenesisJournal of Hematology & Oncology, 2019
- Exosome-mediated transfer of IncRUNX2-AS1 from multiple myeloma cells to MSCs contributes to osteogenesisOncogene, 2018
- Sp1 Plays an Important Role in Vascular Calcification Both In Vivo and In VitroJournal of the American Heart Association, 2018
- The Effects of BMP-2, miR-31, miR-106a, and miR-148a on Osteogenic Differentiation of MSCs Derived from Amnion in Comparison with MSCs Derived from the Bone MarrowStem Cells International, 2017
- The RNA-Binding Protein SYNCRIP Is a Component of the Hepatocyte Exosomal Machinery Controlling MicroRNA SortingCell Reports, 2016
- Involvement of multiple myeloma cell-derived exosomes in osteoclast differentiationOncotarget, 2015
- Interferon-β Induced microRNA-129-5p Down-Regulates HPV-18 E6 and E7 Viral Gene Expression by Targeting SP1 in Cervical Cancer CellsPLOS ONE, 2013
- Myeloma plasma cells alter the bone marrow microenvironment by stimulating the proliferation of mesenchymal stromal cellsHaematologica, 2013
- ABCC5 supports osteoclast formation and promotes breast cancer metastasis to boneBreast Cancer Research, 2012
- A program of microRNAs controls osteogenic lineage progression by targeting transcription factor Runx2Proceedings of the National Academy of Sciences of the United States of America, 2011