Granulocyte-macrophage colony-stimulating factor-dependent CD11c-positive cells differentiate into active osteoclasts.

Ruef, Nina; Dolder, Silvia; Aeberli, Daniel; Seitz, Michael; Balani, Deepak; Hofstetter, Wilhelm (2017). Granulocyte-macrophage colony-stimulating factor-dependent CD11c-positive cells differentiate into active osteoclasts. Bone, 97, pp. 267-277. Elsevier 10.1016/j.bone.2017.01.036

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Levels of circulating cytokines are elevated in inflammatory diseases. Previously, it was shown that interleukin (IL-)17A, in synergism with 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] and tumor necrosis factor α (TNFα), induces the release of granulocyte-macrophage colony-stimulating factor (GM-CSF) by murine osteoblasts in vitro. In this study, we further analyzed the effects of GM-CSF on osteoclast development in vitro. The effects of IL-17A, TNFα, and 1,25(OH)2D3 on the regulation of osteoclast development were investigated in cocultures of bone marrow-derived osteoclast progenitor cells (OPC) and mouse calvarial osteoblasts. Additionally, OPC were grown for 3days in media containing macrophage colony-stimulating factor (M-CSF), GM-CSF, or M-CSF/GM-CSF. Subsequently, the osteoclastogenic potential and the capacity to dissolve amorphous calcium phosphate were assessed in each of the three populations of OPC. IL-17A, in synergism with TNFα and 1,25(OH)2D3, inhibited the development of osteoclasts in cocultures by stimulating the osteoblast lineage cells to release GM-CSF. GM-CSF-treated OPC expressed traits characteristic of dendritic cells. Upon removal of GM-CSF and supplementation of the culture media with M-CSF/RANKL, the cells lost their dendritic cell characteristics and differentiated into osteoclasts. OPC pretreated with GM-CSF and M-CSF/GM-CSF exhibited delayed development to osteoclasts and an extended proliferation phase. Elevated levels of GM-CSF in systemic inflammatory diseases may cause an expansion of the OPC pools in the bone, bone marrow, and blood. Upon homing to the bone, this may lead to an increase in the number of osteoclasts and in bone resorption.

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