PMID- 32835939 OWN - NLM STAT- MEDLINE DCOM- 20210803 LR - 20210803 IS - 1532-3072 (Electronic) IS - 0040-8166 (Linking) VI - 67 DP - 2020 Dec TI - The effective role of sodium copper chlorophyllin on the dysfunction of bone marrow mesenchymal stem cells in multiple myeloma via regulating TGF-beta1. PG - 101406 LID - S0040-8166(20)30136-1 [pii] LID - 10.1016/j.tice.2020.101406 [doi] AB - BACKGROUND: The osteoblast differentiation of bone marrow-derived stem cells (BMSCs) is impaired in multiple myeloma (MM). We investigated the effects of sodium copper chlorophyllin (SCC) on osteoblast differentiation ability of BMSCs from MM. METHODS: Clinical bone marrow samples were collected. Fluorescence Activated Cell Sorter (FACS) was used to identify surface markers of BMSCs. BMSCs were treated with different concentrations of SCC and cell viability was detected by MTT assay. Relative mRNA and protein expressions of transforming growth factor-beta1 (TGF-beta1), SMAD2/3, osteogenic differentiation indicators (RUNX2 and OCN) were measured by quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot. Alkaline phosphatase (ALP) was stained for activity detection. Formation of calcium nodus of BMSCs was examined by Alizarin Red S staining. RESULTS: CD90 and CD105 were high-expressed, but CD34 and CD45 were not expressed in BMSCs. BMSCs in MM group showed a lower expression of TGF-beta1 and a lower degree of osteogenic differentiation. SCC enhanced activities of BMSCs, ALP activity, and formation of calcium nodus, activated TGF-beta1, SMAD2/3 pathway and increased RUNX2 and OCN expressions in BMSCs. Silencing TGF-beta1 reversed the effects of SCC on BMSCs in MM. CONCLUSION: SCC could effectively improve the proliferation and osteogenic differentiation of BMSCs in MM through regulating TGF-beta1. CI - Copyright (c) 2020 Elsevier Ltd. All rights reserved. FAU - Su, Chuanyong AU - Su C AD - Department of Hematology, Tongde Hospital of Zhejiang Province, No. 234, Gucui Road, Xihu District, Hangzhou, Zhejiang Province, 310012, China. FAU - Tao, Diehong AU - Tao D AD - Department of Hematology, Tongde Hospital of Zhejiang Province, No. 234, Gucui Road, Xihu District, Hangzhou, Zhejiang Province, 310012, China. FAU - Ren, Li AU - Ren L AD - Department of Hematology, Tongde Hospital of Zhejiang Province, No. 234, Gucui Road, Xihu District, Hangzhou, Zhejiang Province, 310012, China. FAU - Guo, Shuping AU - Guo S AD - Department of Hematology, Tongde Hospital of Zhejiang Province, No. 234, Gucui Road, Xihu District, Hangzhou, Zhejiang Province, 310012, China. FAU - Zhou, Wenfei AU - Zhou W AD - Department of Hematology, Tongde Hospital of Zhejiang Province, No. 234, Gucui Road, Xihu District, Hangzhou, Zhejiang Province, 310012, China. FAU - Wu, Haiying AU - Wu H AD - Department of Hematology, Tongde Hospital of Zhejiang Province, No. 234, Gucui Road, Xihu District, Hangzhou, Zhejiang Province, 310012, China. FAU - Jiang, Huifang AU - Jiang H AD - Department of Hematology, Tongde Hospital of Zhejiang Province, No. 234, Gucui Road, Xihu District, Hangzhou, Zhejiang Province, 310012, China. Electronic address: huifang_jhfa@163.com. LA - eng PT - Journal Article DEP - 20200707 PL - Scotland TA - Tissue Cell JT - Tissue & cell JID - 0214745 RN - 0 (Biomarkers) RN - 0 (Chlorophyllides) RN - 0 (Core Binding Factor Alpha 1 Subunit) RN - 0 (RNA, Small Interfering) RN - 0 (Smad2 Protein) RN - 0 (Smad3 Protein) RN - 0 (Transforming Growth Factor beta1) RN - 104982-03-8 (Osteocalcin) RN - EC 3.1.3.1 (Alkaline Phosphatase) RN - EEM82VOY7C (chlorophyllin) SB - IM MH - Alkaline Phosphatase/metabolism MH - Biomarkers/metabolism MH - Bone Marrow Cells/drug effects/*metabolism MH - Cell Differentiation/drug effects MH - Cell Survival/drug effects MH - Chlorophyllides/*pharmacology MH - Core Binding Factor Alpha 1 Subunit/metabolism MH - Gene Silencing/drug effects MH - Humans MH - Mesenchymal Stem Cells/drug effects/*metabolism MH - Multiple Myeloma/*metabolism/pathology MH - Osteocalcin/metabolism MH - Osteogenesis/drug effects MH - RNA, Small Interfering/metabolism MH - Signal Transduction/drug effects MH - Smad2 Protein/metabolism MH - Smad3 Protein/metabolism MH - Transforming Growth Factor beta1/*metabolism OTO - NOTNLM OT - Bone marrow mesenchymal stem cells OT - Osteogenic differentiation OT - Sodium copper chlorophyllin OT - TGF-beta1 EDAT- 2020/08/25 06:00 MHDA- 2021/08/04 06:00 CRDT- 2020/08/25 06:00 PHST- 2020/03/11 00:00 [received] PHST- 2020/07/02 00:00 [revised] PHST- 2020/07/06 00:00 [accepted] PHST- 2020/08/25 06:00 [pubmed] PHST- 2021/08/04 06:00 [medline] PHST- 2020/08/25 06:00 [entrez] AID - S0040-8166(20)30136-1 [pii] AID - 10.1016/j.tice.2020.101406 [doi] PST - ppublish SO - Tissue Cell. 2020 Dec;67:101406. doi: 10.1016/j.tice.2020.101406. Epub 2020 Jul 7.