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Cancer Cell International
Published in: Cancer Cell International 1/2014

Open Access 01-12-2014 | Primary research

Osteoblast inhibition by chemokine cytokine ligand3 in myeloma-induced bone disease

Authors: Rong Fu, Hui Liu, Sijie Zhao, Yihao Wang, Lijuan Li, Shan Gao, Erbao Ruan, Guojin Wang, Huaquan Wang, Jia Song, Zonghong Shao

Published in: Cancer Cell International | Issue 1/2014

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Abstract

Background

Multiple myeloma is a hematologic malignancy characterized by the accumulation of monoclonal plasma cells in the bone marrow. A common manifestation of the disease is myeloma bone disease (MBD), which is caused by increased osteoclastic bone resorption and decreased bone formation. The chemokine cytokine ligand 3 (CCL3) is a pro-inflammatory protein and chemokine that stimulates osteoclasts in MBD. However, little is known about the effect of CCL3 on osteoblasts (OB).

Methods

The OBs are induced from patients with MBD and healthy donors, cultured in vitro, and identified by histochemistry. The effects of CCL3 and CCL3 antibody on the OBs in vitro are observed. The CCL3 receptor (CCR1), osteocalcin (OCN), runt-related transcription factor 2 (Runx2), and osterix (Osx) are detected using flow cytometry, enzyme-linked immunosorbent assay, and real-time PCR.

Results

Proliferation and osteogenic potential of the OB in patients with MBD are suppressed. Moreover, the CCR1 expression is significantly higher in patients with MBD than in normal controls. The OCN level, quantity of calcium nodules, and Runx2 and Osx levels decrease after CCL3 stimulation, which indicates that CCL3 inhibits OB function. Furthermore, CCL3 antibody partially restores OB activity through the upregulation of the OCN, Runx2, and Osx.

Conclusions

CCL3 contributes to the OB/OC imbalance by inhibiting OB differentiation and function in MBD.
Appendix
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Metadata
Title
Osteoblast inhibition by chemokine cytokine ligand3 in myeloma-induced bone disease
Authors
Rong Fu
Hui Liu
Sijie Zhao
Yihao Wang
Lijuan Li
Shan Gao
Erbao Ruan
Guojin Wang
Huaquan Wang
Jia Song
Zonghong Shao
Publication date
01-12-2014
Publisher
BioMed Central
Published in
Cancer Cell International / Issue 1/2014
Electronic ISSN: 1475-2867
DOI
https://doi.org/10.1186/s12935-014-0132-6

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