Bone marrow stromal cells (BMSCs) play a critical role in multiple myeloma (MM) pathogenesis by cell contact, and secretion of cytokines, growth factors and extracellular vesicles. Exosomes are secreted by almost all cell types and are recently reported to mediate local cell-to-cell cross-talk by transferring messenger RNAs, LncRNAs, and proteins. Compelling studies have identified BMSC-derived exosomes induce proliferation, migration, survival, and drug resistance of MM cells. However, whether MM cell-derived exosome also plays a role in function in BMSC remains unclear. Here we investigated the effect of MM cell-derived exosomes on the interleukin (IL)-6 secretion and osteoblastic differentiation capability of BMSC from patients with MM. Furthermore we investigated the IL-6 secretion relative regulation protein APE1 and NF-kB and osteoblastic differentiation protein Runx2 (runt-related gene 2), Osterix and osteocalcin (OCN). Our results showed that MM cell-derived exosomes promoted IL-6 secretion and suppressed osteoblastic differentiation and mineralization of BMSCs. Mechanistically, we demonstrated that MM cell-derived exosomes lead to an increase in APE1 and NF-kB and a reduction in Runx2, Osterix and OCN in BMSCs. Taken together, MM cell-derived exosomes induce the secretion of IL-6 and poor osteoblastic differentiation of BMSCs.
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Contributors ZL, HL and RF designed this research. ZL and YL carried out most of the experiments, analyzed the data, drew the figures and drafted this manuscript. JC and QS helped with the cell culture, western blot experiments, qRT-PCR and the FCM. JS helped check the manuscript and figures. All authors read and approved the final manuscript.
Funding The study was supported by the National Natural Science Foundation of China (grant no 81770110), the Tianjin Municipal Natural Science Foundation (grant no 15JCYBJC24300, 2018KJ043, 2018KJ045 and 18JCQNJC80400) and the Youth Incubation Fund of Tianjin Medical University General Hospital (ZYYFY 2016006). Tianjin Institute of Lung Cancer provided support in the lab.
Competing interests None declared.
Ethics approval This study was approved by the Ethics Committee of Tianjin Medical University (IRB-2016-YX-081).
Provenance and peer review Not commissioned; externally peer reviewed.
Patient consent for publication Not required.
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