Abstract
BackgroundMultiple 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).MethodsThe 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.ResultsProliferation 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.ConclusionsCCL3 contributes to the OB/OC imbalance by inhibiting OB differentiation and function in MBD.
Highlights
Multiple myeloma is a hematologic malignancy characterized by the accumulation of monoclonal plasma cells in the bone marrow
This study investigates the effect of chemokine cytokine ligand 3 (CCL3) on the OB of patients with myeloma bone disease (MBD)
The OB growth curve showed that the proliferative rate of the OB from the patients with MBD was constitutively suppressed (Figure 1D)
Summary
Multiple myeloma is a hematologic malignancy characterized by the accumulation of monoclonal plasma cells in the bone marrow. Little is known about the effect of CCL3 on osteoblasts (OB). Majority of patients with multiple myeloma (MM) suffer from bone osteolytic lesions called myeloma bone disease (MBD). The osteolytic lesions rarely heal because of the MM-induced suppression of osteoblast (OB) activity even when the patients have prolonged remission and the MM cells are not detectable. The bone marrow stromal cells, OBs, osteoclasts (OC), endothelial cells and immune cells in a normal condition regulate each other’s function through direct data are presently available on the effects of CCL3 on OB. This study investigates the effect of CCL3 on the OB of patients with MBD
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