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

Autor: Er-bao Ruan, Shan Gao, Jia Song, Guojin Wang, Huaquan Wang, Yihao Wang, Hui Liu, Zonghong Shao, Lijuan Li, Sijie Zhao, Rong Fu
Jazyk: angličtina
Rok vydání: 2014
Předmět:
Zdroj: Cancer Cell International
ISSN: 1475-2867
Popis: 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.
Databáze: OpenAIRE
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