Related Experiment Video
Updated: Aug 17, 2026

Effect of Anti-c-fms Antibody on Osteoclast Formation and Proliferation of Osteoclast Precursor In Vitro
Published on: March 18, 2019
Myeloma cells block RUNX2/CBFA1 activity in human bone marrow osteoblast progenitors and inhibit osteoblast formation
Nicola Giuliani1, Simona Colla, Francesca Morandi
1Laboratory of Hematology, Hematology and Bone Marrow Transplantation (BMT) Center, Department of Internal Medicine and Biomedical Science, University of Parma, Parma, Italy. nicola.giuliani@unipr.it
Abstract:
Decreased bone formation contributes to the development of bone lesions in multiple myeloma (MM) patients. In this study, we have investigated the effects of myeloma cells on osteoblast formation and differentiation and the potential role of the critical osteoblast transcription factor RUNX2/CBFA1 (Runt-related transcription factor 2/core-binding factor Runt domain alpha subunit 1) in the inhibition of osteoblastogenesis in MM. We found that human myeloma cells suppress the formation of human osteoblast progenitors in bone marrow (BM) cultures. Moreover, an inhibitory effect on osteocalcin, alkaline phosphatase, collagen I mRNA, protein expression, and RUNX2/CBFA1 activity by human preosteoblastic cells was observed in cocultures with myeloma cells. The inhibitory effect was more pronounced in the cell-to-cell contact conditions compared with those without the contact and involved the very late antigen 4 (VLA-4) integrin system. Among the soluble osteoblast inhibitors screened, we show the potential contribution of interleukin-7 (IL-7) in the inhibitory effect on osteoblast formation and RUNX2/CBFA1 activity by human myeloma cells in coculture. Finally, our in vitro results were supported in vivo by the finding of a significant reduction in the number of Runx2/Cbfa1-positive cells in the BM biopsies of patients with MM who had osteolytic lesions compared with those who did not have bone lesions, suggesting the critical involvement of RUNX2/CBFA1 in the decreased bone formation in MM.
Insights
Multiple myeloma cells inhibit bone formation by suppressing osteoblast development and the key transcription factor RUNX2/CBFA1. This leads to reduced bone in patients, impacting skeletal health.
Area of Science:
- Bone Biology
- Hematology
- Oncology
Background:
- Multiple myeloma (MM) is characterized by decreased bone formation, leading to osteolytic lesions.
- The transcription factor RUNX2/CBFA1 is critical for osteoblast differentiation and bone formation.
Purpose of the Study:
- To investigate how myeloma cells affect osteoblastogenesis.
- To determine the role of RUNX2/CBFA1 in myeloma-associated bone loss.
Main Methods:
- Co-culture of human myeloma cells with human osteoblast progenitors.
- Assessment of osteoblast markers (osteocalcin, alkaline phosphatase, collagen I) and RUNX2/CBFA1 activity.
- Involvement of cell-to-cell contact and the VLA-4 integrin system were examined.
- Screening of soluble inhibitors, including IL-7.
- Analysis of bone marrow biopsies from MM patients.
Main Results:
- Myeloma cells suppressed osteoblast progenitor formation and differentiation in vitro.
- Inhibition of osteoblast markers and RUNX2/CBFA1 activity was observed, particularly with cell contact via VLA-4.
- Interleukin-7 (IL-7) was identified as a potential soluble inhibitor.
- Reduced numbers of RUNX2/CBFA1-positive cells were found in MM patients with osteolytic lesions.
Conclusions:
- Myeloma cells directly inhibit osteoblast formation and differentiation.
- RUNX2/CBFA1 plays a crucial role in the decreased bone formation seen in multiple myeloma.
- Cell-to-cell contact and IL-7 contribute to this inhibitory process.
Related Concept Videos
Differentiation of Common Myeloid Progenitor Cells
Osteoclasts in Bone Remodeling
Abnormal Proliferation
