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Published on: October 31, 2017
Induction of apoptosis of monocyte-macrophage lineage cells by 5-S-GAD
M Hijikata1, H N Matsumoto, A Kobayashi
1Graduate School of Pharmaceutical Sciences, University of Tokyo, Bunkyo-ku, Tokyo, Japan.
Abstract:
We found that 5-S-GAD, an insect-derived antibacterial peptide, inhibited murine osteoclast formation in vitro. We examined the specific time point of the inhibitory action of 5-S-GAD on osteoclast formation and found that it mainly suppressed differentiation of osteoclasts in the middle of the culture period. Using HL60 cells that are able to differentiate into multinucleated macrophage-like cells, we found that 5-S-GAD induced apoptosis of HL60 cells by producing H(2)O(2). Thus, the inhibition of osteoclast formation by 5-S-GAD could be, in part, due to apoptosis of the cells of an osteoclast lineage.
Insights
The insect peptide 5-S-GAD inhibits bone-resorbing osteoclast formation by inducing apoptosis in precursor cells. This antibacterial peptide shows potential for modulating bone remodeling processes.
Area of Science:
- Biochemistry
- Immunology
- Cell Biology
Background:
- Osteoclasts are crucial for bone resorption and remodeling.
- Dysregulation of osteoclast activity is implicated in bone diseases.
- Novel therapeutic targets for modulating osteoclastogenesis are needed.
Purpose of the Study:
- To investigate the effect of 5-S-GAD, an insect-derived antibacterial peptide, on murine osteoclast formation.
- To determine the mechanism by which 5-S-GAD inhibits osteoclastogenesis.
Main Methods:
- In vitro culture of murine bone marrow cells to assess osteoclast formation.
- Treatment with 5-S-GAD at different time points during differentiation.
- Analysis of HL60 cell apoptosis induced by 5-S-GAD, including hydrogen peroxide (H2O2) production measurement.
Main Results:
- 5-S-GAD significantly inhibited murine osteoclast formation in vitro.
- The peptide primarily suppressed osteoclast differentiation during the mid-culture period.
- 5-S-GAD induced apoptosis in HL60 cells, a model for osteoclast precursor cells, via hydrogen peroxide production.
Conclusions:
- 5-S-GAD exhibits inhibitory effects on osteoclast formation.
- The mechanism involves inducing apoptosis in osteoclast lineage cells.
- 5-S-GAD represents a potential therapeutic agent for bone disorders characterized by excessive osteoclast activity.
