Related Experiment Video
Updated: Apr 28, 2026
Stimulation of Notch Signaling in Mouse Osteoclast Precursors
Published on: February 28, 2017
Notch pathway inhibition controls myeloma bone disease in the murine MOPC315.BM model
R Schwarzer1, N Nickel1, J Godau1
1Department of Hematology, Oncology and Tumor Immunology, Campus Virchow-Klinikum, Charité-Universitätsmedizin Berlin, Berlin, Germany.
Abstract:
Despite evidence that deregulated Notch signalling is a master regulator of multiple myeloma (MM) pathogenesis, its contribution to myeloma bone disease remains to be resolved. Notch promotes survival of human MM cells and triggers human osteoclast activity in vitro. Here, we show that inhibition of Notch through the γ-secretase inhibitor XII (GSI XII) induces apoptosis of murine MOPC315.BM myeloma cells with high Notch activity. GSI XII impairs murine osteoclast differentiation of receptor activator of NF-κB ligand (RANKL)-stimulated RAW264.7 cells in vitro. In the murine MOPC315.BM myeloma model GSI XII has potent anti-MM activity and reduces osteolytic lesions as evidenced by diminished myeloma-specific monoclonal immunoglobulin (Ig)-A serum levels and quantitative assessment of bone structure changes via high-resolution microcomputed tomography scans. Thus, we suggest that Notch inhibition through GSI XII controls myeloma bone disease mainly by targeting Notch in MM cells and possibly in osteoclasts in their microenvironment. We conclude that Notch inhibition is a valid therapeutic strategy in MM.
Insights
Notch inhibition effectively targets multiple myeloma (MM) cells and reduces bone lesions. This study shows γ-secretase inhibitor XII (GSI XII) controls myeloma bone disease by targeting Notch signaling in MM cells and osteoclasts.
Area of Science:
- Oncology
- Cell Biology
- Biochemistry
Background:
- Deregulated Notch signaling is implicated in multiple myeloma (MM) pathogenesis.
- Notch signaling promotes MM cell survival and osteoclast activity.
- The role of Notch in myeloma bone disease requires further elucidation.
Purpose of the Study:
- To investigate the therapeutic potential of Notch inhibition in MM bone disease.
- To determine the effects of γ-secretase inhibitor XII (GSI XII) on MM cells and osteoclasts.
Main Methods:
- Treatment of murine MOPC315.BM myeloma cells with GSI XII.
- Assessment of osteoclast differentiation in RANKL-stimulated RAW264.7 cells with GSI XII.
- Evaluation of anti-MM activity and bone lesion reduction in a murine MOPC315.BM myeloma model using GSI XII.
Main Results:
- GSI XII induced apoptosis in high-Notch-activity murine MM cells.
- GSI XII impaired osteoclast differentiation in vitro.
- GSI XII demonstrated potent anti-MM activity and reduced osteolytic lesions in vivo, evidenced by decreased IgA levels and microcomputed tomography scans.
Conclusions:
- Notch inhibition via GSI XII is a promising therapeutic strategy for multiple myeloma.
- GSI XII controls myeloma bone disease by targeting Notch signaling in MM cells and potentially osteoclasts.
- Further research into Notch inhibition for MM treatment is warranted.
More Related Videos
10:04Establishment of a Human Multiple Myeloma Xenograft Model in the Chicken to Study Tumor Growth, Invasion and Angiogenesis
Published on: May 1, 2015
08:00A Detailed Protocol for Characterizing the Murine C1498 Cell Line and its Associated Leukemia Mouse Model
Published on: October 14, 2016
Related Concept Videos
03:14Notch Signaling Pathway
The Notch gene came into the limelight in 1914 after the discovery that its mutation in Drosophila melanogaster leads to a serrated (or "notched") wing margin phenotype. It was not...
03:14Notch Signaling Pathway
02:43Mouse Models of Cancer Study
The development of transgenic, knockout, and knock-in mice has led to an exponential increase in their use as model organisms in research,...
01:12Role Of Notch Signalling In Intestinal Stem Cell Renewal
Direct cell-to-cell contact is needed for the activation of Notch signaling. The signal is initiated when a notch ligand binds to a receptor on an adjacent cell, also...