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Updated: Mar 30, 2026
Differentiation of Functional Osteoclasts from Human Peripheral Blood CD14+ Monocytes
Published on: January 27, 2023
Inhibition of osteoclast differentiation by overexpression of NDRG2 in monocytes
Kyeongah Kang1, Sorim Nam1, Bomi Kim1
1Department of Biological Sciences and the Research Center for Women's Disease, Sookmyung Women's University, Seoul 140-742, Republic of Korea.
Abstract:
N-Myc downstream-regulated gene 2 (NDRG2), a member of the NDRG family of differentiation-related genes, has been characterized as a regulator of dendritic cell differentiation from monocytes, CD34(+) progenitor cells, and myelomonocytic leukemic cells. In this study, we show that NDRG2 overexpression inhibits the differentiation of U937 cells into osteoclasts in response to stimulation with a combination of macrophage colony-stimulating factor (M-CSF) and soluble receptor activator of NF-κB ligand (RANKL). U937 cells stably expressing NDRG2 are unable to differentiate into multinucleated osteoclast-like cells and display reduced tartrate-resistant acid phosphatase (TRAP) activity and resorption pit formation. Furthermore, NDRG2 expression significantly suppresses the expression of genes that are crucial for the proliferation, survival, differentiation, and function of osteoclasts, including c-Fos, Atp6v0d2, RANK, and OSCAR. The activation of ERK1/2 and p38 is also inhibited by NDRG2 expression during osteoclastogenesis, and the inhibition of osteoclastogenesis by NDRG2 correlates with the down-regulation of the expression of the transcription factor PU.1. Taken together, our results suggest that the expression of NDRG2 potentially inhibits osteoclast differentiation and plays a role in modulating the signal transduction pathway responsible for osteoclastogenesis.
Insights
N-Myc downstream-regulated gene 2 (NDRG2) inhibits osteoclast differentiation by suppressing key genes and signaling pathways. This finding suggests NDRG2 plays a role in regulating bone cell formation.
Area of Science:
- Molecular Biology
- Cell Biology
- Immunology
Background:
- N-Myc downstream-regulated gene 2 (NDRG2) is a differentiation-related gene.
- NDRG2 regulates dendritic cell differentiation.
- Osteoclasts are crucial for bone remodeling.
Purpose of the Study:
- To investigate the role of NDRG2 in osteoclast differentiation.
- To determine the molecular mechanisms by which NDRG2 affects osteoclastogenesis.
Main Methods:
- Overexpression of NDRG2 in U937 cells.
- Stimulation of osteoclast differentiation with M-CSF and RANKL.
- Analysis of osteoclast markers (TRAP), resorption, gene expression, and signaling pathways (ERK1/2, p38).
Main Results:
- NDRG2 overexpression inhibited U937 cell differentiation into osteoclasts.
- NDRG2 reduced TRAP activity, resorption pit formation, and expression of key osteoclast genes (c-Fos, Atp6v0d2, RANK, OSCAR).
- NDRG2 suppressed ERK1/2 and p38 activation and down-regulated PU.1 expression.
Conclusions:
- NDRG2 expression inhibits osteoclast differentiation.
- NDRG2 modulates the signal transduction pathways involved in osteoclastogenesis.
- NDRG2 may play a role in bone homeostasis and diseases involving abnormal osteoclast activity.
