title: IL-3 is a potential inhibitor of osteoblast differentiation in multiple myeloma.
abstract: 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.
authors.affiliation: Department of Medicine, University of Pittsburgh, Pittsburgh, PA, USA.
authors.forename: Lori A
authors.initials: LA
authors.lastname: Ehrlich
authors.forename: Ho Yeon
authors.initials: HY
authors.lastname: Chung
authors.forename: Irene
authors.initials: I
authors.lastname: Ghobrial
authors.forename: Sun Jin
authors.initials: SJ
authors.lastname: Choi
authors.forename: Francesca
authors.initials: F
authors.lastname: Morandi
authors.forename: Simona
authors.initials: S
authors.lastname: Colla
authors.forename: Vittorio
authors.initials: V
authors.lastname: Rizzoli
authors.forename: G David
authors.initials: GD
authors.lastname: Roodman
authors.forename: Nicola
authors.initials: N
authors.lastname: Giuliani
mesh_terms: 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
chemical_list: D007377:Interleukin-3; D017493:Leukocyte Common Antigens