title: Osteoblast inhibition by chemokine cytokine ligand3 in myeloma-induced bone disease.
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.
authors.affiliation: Department of Hematology, Tianjin Medical University General Hospital, 154 Anshao Street, Heping District, Tianjin 300052 PR China.
authors.forename: Rong
authors.initials: R
authors.lastname: Fu
authors.affiliation: Department of Hematology, Tianjin Medical University General Hospital, 154 Anshao Street, Heping District, Tianjin 300052 PR China.
authors.forename: Hui
authors.initials: H
authors.lastname: Liu
authors.affiliation: Department of Hematology, Tianjin Medical University General Hospital, 154 Anshao Street, Heping District, Tianjin 300052 PR China.
authors.forename: Sijie
authors.initials: S
authors.lastname: Zhao
authors.affiliation: Department of Hematology, Tianjin Medical University General Hospital, 154 Anshao Street, Heping District, Tianjin 300052 PR China.
authors.forename: Yihao
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Hematology, Tianjin Medical University General Hospital, 154 Anshao Street, Heping District, Tianjin 300052 PR China.
authors.forename: Lijuan
authors.initials: L
authors.lastname: Li
authors.affiliation: Department of Hematology, Tianjin Medical University General Hospital, 154 Anshao Street, Heping District, Tianjin 300052 PR China.
authors.forename: Shan
authors.initials: S
authors.lastname: Gao
authors.affiliation: Department of Hematology, Tianjin Medical University General Hospital, 154 Anshao Street, Heping District, Tianjin 300052 PR China.
authors.forename: Erbao
authors.initials: E
authors.lastname: Ruan
authors.affiliation: Department of Hematology, Tianjin Medical University General Hospital, 154 Anshao Street, Heping District, Tianjin 300052 PR China.
authors.forename: Guojin
authors.initials: G
authors.lastname: Wang
authors.affiliation: Department of Hematology, Tianjin Medical University General Hospital, 154 Anshao Street, Heping District, Tianjin 300052 PR China.
authors.forename: Huaquan
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Hematology, Tianjin Medical University General Hospital, 154 Anshao Street, Heping District, Tianjin 300052 PR China.
authors.forename: Jia
authors.initials: J
authors.lastname: Song
authors.affiliation: Department of Hematology, Tianjin Medical University General Hospital, 154 Anshao Street, Heping District, Tianjin 300052 PR China.
authors.forename: Zonghong
authors.initials: Z
authors.lastname: Shao
keywords: Chemokine cytokine ligand 3; Myeloma bone disease; Osteoblast; Osterix; Runx2