The effective role of sodium copper chlorophyllin on the dysfunction of bone marrow mesenchymal stem cells in multiple myeloma via regulating TGF-β1

Tissue Cell. 2020 Dec:67:101406. doi: 10.1016/j.tice.2020.101406. Epub 2020 Jul 7.

Abstract

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-β1 (TGF-β1), 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-β1 and a lower degree of osteogenic differentiation. SCC enhanced activities of BMSCs, ALP activity, and formation of calcium nodus, activated TGF-β1, SMAD2/3 pathway and increased RUNX2 and OCN expressions in BMSCs. Silencing TGF-β1 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-β1.

Keywords: Bone marrow mesenchymal stem cells; Osteogenic differentiation; Sodium copper chlorophyllin; TGF-β1.

MeSH terms

  • Alkaline Phosphatase / metabolism
  • Biomarkers / metabolism
  • Bone Marrow Cells / drug effects
  • Bone Marrow Cells / metabolism*
  • Cell Differentiation / drug effects
  • Cell Survival / drug effects
  • Chlorophyllides / pharmacology*
  • Core Binding Factor Alpha 1 Subunit / metabolism
  • Gene Silencing / drug effects
  • Humans
  • Mesenchymal Stem Cells / drug effects
  • Mesenchymal Stem Cells / metabolism*
  • Multiple Myeloma / metabolism*
  • Multiple Myeloma / pathology
  • Osteocalcin / metabolism
  • Osteogenesis / drug effects
  • RNA, Small Interfering / metabolism
  • Signal Transduction / drug effects
  • Smad2 Protein / metabolism
  • Smad3 Protein / metabolism
  • Transforming Growth Factor beta1 / metabolism*

Substances

  • Biomarkers
  • Chlorophyllides
  • Core Binding Factor Alpha 1 Subunit
  • RNA, Small Interfering
  • Smad2 Protein
  • Smad3 Protein
  • Transforming Growth Factor beta1
  • Osteocalcin
  • Alkaline Phosphatase
  • chlorophyllin