The effect of macrophage-colony stimulating factor and other humoral factors (interleukin-1,-3,-6, and-11, tumor necrosis factor-α, and granulocyte macrophage-colony stimulating factor) on human osteoclast formation from circulating cells

Macrophage-colony stimulating factor (M-CSF) is an essential requirement for human osteoclast formation, but its effect on the proliferation and differentiation of circulating osteoclast precursor cells is unknown. Other growth factors and cytokines are also known to support/stimulate osteoclast formation fi om mouse marrow precursors, but it is not certain whether those factors similarly influence human osteoclast formation. In this study, human monocytes were cocultured with osteoblast-like UMR-106 cells on coverslips and dentine slices for up to 21 days in the presence of 1,25 dihydroxyvitamin D-3 (10(-7) mol/L), dexamethasone (10(-8) mol/L), and various concentrations of either M-CSF or other humoral factors (interleukin [IL]-1 beta, IL-3, IL-6, and IL-11; tumor necrosis fartor-alpha [TNF-alpha]; and granulocyte macrophage [GM]-CSF). The effect on osteoclast formation,vas assessed by tartrate-resistant acid phosphatase (TRAP) and vitronectin receptor staining and lacunar bone resorption. The results of time-course and proliferation studies showed that M-CSF stimulated both the proliferative and differentiation stages of human osteoclast formation from circulating osteoclast precursors in a dose-dependent manner. A high concentration of M-CSF (100 ng/mL) did not inhibit osteoclast formation. IL-3 and GM-CSF were also capable of stimulating human osteoclast formation, although these growth factors were much less potent than M-CSF. IL-3- and GM-CSF-stimulated osteoclast formation was inhibited by an antibody specific for human M-CSF. Osteoclast formation and lacunar resorption was not seen when either TNF-alpha, IL-1 beta, IL-6 (+ soluble IL-6 receptor), or IL-11 was substituted for M-CSF during coculture, Those results confirm that CII-CSF is essential for human osteoclast formation from circulating mononuclear precursors, and also show's that IL-3 and GM-CSF may support osteoclast differentiation via the stimulation of M-CSF production by human monocytes. (Bone 28:261-267; 2001) (C) 2001 by Elsevier Science Inc. All rights reserved.