PMID- 31784427 OWN - NLM STAT- MEDLINE DCOM- 20210430 LR - 20210430 IS - 1708-8267 (Electronic) IS - 1081-5589 (Print) IS - 1081-5589 (Linking) VI - 68 IP - 1 DP - 2020 Jan TI - Multiple myeloma-derived exosomes inhibit osteoblastic differentiation and improve IL-6 secretion of BMSCs from multiple myeloma. PG - 45-51 LID - 10.1136/jim-2019-001010 [doi] AB - 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. CI - (c) American Federation for Medical Research 2020. Re-use permitted under CC BY-NC. No commercial re-use. Published by BMJ. FAU - Liu, Zhaoyun AU - Liu Z AUID- ORCID: 0000-0002-2730-1562 AD - Hematology department, Tianjin Medical University General Hospital, Tianjin, China. FAU - Liu, Hui AU - Liu H AD - Hematology department, Tianjin Medical University General Hospital, Tianjin, China. FAU - Li, Yanqi AU - Li Y AD - Hematology department, Tianjin Medical University General Hospital, Tianjin, China. FAU - Shao, Qin AU - Shao Q AD - Hematology department, Tianjin Medical University General Hospital, Tianjin, China. FAU - Chen, Jin AU - Chen J AD - Hematology department, Tianjin Medical University General Hospital, Tianjin, China. FAU - Song, Jia AU - Song J AD - Hematology department, Tianjin Medical University General Hospital, Tianjin, China. FAU - Fu, Rong AU - Fu R AD - Hematology department, Tianjin Medical University General Hospital, Tianjin, China. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20191128 PL - England TA - J Investig Med JT - Journal of investigative medicine : the official publication of the American Federation for Clinical Research JID - 9501229 RN - 0 (Interleukin-6) SB - IM MH - Aged MH - Aged, 80 and over MH - *Cell Differentiation MH - Cell Line, Tumor MH - Cells, Cultured MH - Enzyme-Linked Immunosorbent Assay MH - Exosomes/*metabolism/physiology/ultrastructure MH - Female MH - Humans MH - Interleukin-6/*metabolism MH - Male MH - Mesenchymal Stem Cells/*metabolism MH - Microscopy, Electron, Transmission MH - Middle Aged MH - Multiple Myeloma/*metabolism MH - Osteoblasts/*cytology MH - Real-Time Polymerase Chain Reaction PMC - PMC6996099 OTO - NOTNLM OT - hematology COIS- Competing interests: None declared. EDAT- 2019/12/01 06:00 MHDA- 2021/05/01 06:00 PMCR- 2020/02/03 CRDT- 2019/12/01 06:00 PHST- 2019/05/27 00:00 [accepted] PHST- 2019/12/01 06:00 [pubmed] PHST- 2021/05/01 06:00 [medline] PHST- 2019/12/01 06:00 [entrez] PHST- 2020/02/03 00:00 [pmc-release] AID - jim-2019-001010 [pii] AID - 10.1136/jim-2019-001010 [doi] PST - ppublish SO - J Investig Med. 2020 Jan;68(1):45-51. doi: 10.1136/jim-2019-001010. Epub 2019 Nov 28.