Acute Lymphoblastic Leukemia Cells Inhibit the Differentiation of Bone Mesenchymal Stem Cells into Osteoblasts In Vitro by Activating Notch Signaling

Stem Cells International
Gui-Cun YangXiao-Jing Wang

Abstract

The disruption of normal hematopoiesis has been observed in leukemia, but the mechanism is unclear. Osteoblasts originate from bone mesenchymal stem cells (BMSCs) and can maintain normal hematopoiesis. To investigate how leukemic cells inhibit the osteogenic differentiation of BMSCs and the role of Notch signaling in this process, we cocultured BMSCs with acute lymphoblastic leukemia (ALL) cells in osteogenic induction medium. The expression levels of Notch1, Hes1, and the osteogenic markers Runx2, Osteopontin (OPN), and Osteocalcin (OCN) were assessed by real-time RT-PCR and western blotting on day 3. Alkaline phosphatase (ALP) activity was analyzed using an ALP kit, and mineralization deposits were detected by Alizarin red S staining on day 14. And then we treated BMSCs with Jagged1 and anti-Jagged1 neutralizing Ab. The expression of Notch1, Hes1, and the abovementioned osteogenic differentiation markers was measured. Inhibition of the expression of Runx2, OPN, and OCN and reduction of ALP activity and mineralization deposits were observed in BMSCs cocultured with ALL cells, while Notch signal inhibiting rescued these effects. All these results indicated that ALL cells could inhibit the osteogenic differentiation of BMSCs by ...Continue Reading

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Citations

Feb 14, 2016·Lasers in Medical Science·Juliana Rosa Luiz AlonsoJosimeri Hebling
Mar 23, 2017·Biomarkers in Medicine·Gabrielle KarpinskyEwa Bien
Mar 11, 2017·Clinical & Translational Oncology : Official Publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico·S AzizidoostN Saki
Feb 27, 2020·International Journal of Molecular Sciences·Maurizio Mangolini, Ingo Ringshausen
Jun 22, 2017·Case Reports in Cardiology·Ali Sadeghpour TabaeiSepehr Sadeghpour Tabaei
Jul 1, 2021·Calcified Tissue International·Wei HongXiaoya Xu

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Methods Mentioned

BETA
density gradient centrifugation
Polymerase Chain Reaction
PCR
flow cytometry

Software Mentioned

GraphPad Prism

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