IL-3 is a potential inhibitor of osteoblast differentiation in multiple myeloma.
Bone destruction in multiple myeloma is characterized both by markedly increased osteoclastic bone destruction and severely impaired osteoblast activity. We reported that interleukin-3 (IL-3) levels are increased in bone marrow plasma of myeloma patients compared with healthy controls and that IL-3 stimulates osteoclast formation. However, the effects of IL-3 on osteoblasts are unknown. Therefore, to determine if IL-3 inhibits osteoblast growth and differentiation, we treated primary mouse and human marrow stromal cells with IL-3 and assessed osteoblast differentiation. IL-3 inhibited basal and bone morphogenic protein-2 (BMP-2)-stimulated osteoblast formation in a dose-dependent manner without affecting cell growth. Importantly, marrow plasma from patients with high IL-3 levels inhibited osteoblast differentiation, which could be blocked by anti-IL-3. However, IL-3 did not inhibit osteoblast differentiation of osteoblastlike cell lines. In contrast, IL-3 increased the number of CD45+ hematopoietic cells in stromal-cell cultures. Depletion of the CD45+ cells abolished the inhibitory effects of IL-3 on osteoblasts, and reconstitution of the cultures with CD45+ cells restored the capacity of IL-3 to inhibit osteoblast differentiation. These data suggest that IL-3 plays a dual role in the bone destructive process in myeloma by both stimulating osteoclasts and indirectly inhibiting osteoblast formation.
Ehrlich
Lori A
LA
Department of Medicine, University of Pittsburgh, Pittsburgh, PA, USA.
Chung
Ho Yeon
HY
Ghobrial
Irene
I
Choi
Sun Jin
SJ
Morandi
Francesca
F
Colla
Simona
S
Rizzoli
Vittorio
V
Roodman
G David
GD
Giuliani
Nicola
N
D000818:Animals; D001854:Bone Marrow Cells / Q000473:pathology; D002454:Cell Differentiation / Q000187:drug effects; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D006412:Hematopoietic Stem Cells; D006801:Humans; D007377:Interleukin-3 / Q000494:pharmacology*; D017493:Leukocyte Common Antigens; D051379:Mice; D009101:Multiple Myeloma / Q000188:drug therapy / Q000473:pathology*; D010006:Osteoblasts / Q000187:drug effects* / Q000473:pathology; D010010:Osteoclasts / Q000187:drug effects; D017154:Stromal Cells / Q000473:pathology
D007377:Interleukin-3; D017493:Leukocyte Common Antigens