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.

IL-3 is a potential inhibitor of osteoblast differentiation in multiple myeloma / Ehrlich, La; Chung, Hy; Ghobrial, I; Choi, Sj; Morandi, F; Colla, S; Rizzoli, Vittorio; Roodman, Gd; Giuliani, Nicola. - In: BLOOD. - ISSN 0006-4971. - 106:(2005), pp. 1407-1414. [10.1182/blood-2005-03-1080]

IL-3 is a potential inhibitor of osteoblast differentiation in multiple myeloma

RIZZOLI, Vittorio;GIULIANI, Nicola
2005-01-01

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.
2005
IL-3 is a potential inhibitor of osteoblast differentiation in multiple myeloma / Ehrlich, La; Chung, Hy; Ghobrial, I; Choi, Sj; Morandi, F; Colla, S; Rizzoli, Vittorio; Roodman, Gd; Giuliani, Nicola. - In: BLOOD. - ISSN 0006-4971. - 106:(2005), pp. 1407-1414. [10.1182/blood-2005-03-1080]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11381/1631002
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