Multiple roles of M-CSF in human osteoclastogenesis.

Multiple roles of M-CSF in human osteoclastogenesis. Research Abstract Details 

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Multiple roles of M-CSF in human osteoclastogenesis. Abstract Text:

Jason M Hodge,Mark A Kirkland,Geoffrey C Nicholson,Jason M Hodge,Mark A Kirkland,Geoffrey C Nicholson,

Although the critical role of M-CSF in osteoclastogenesis is well documented, there has been no detailed analysis of how it regulates human osteoclast formation and function in vitro. We used a human osteoclastogenesis model employing CFU-GM osteoclast precursors cultured for 14 days on dentine with RANKL, with varying exposure to exogenous human M-CSF. Short-term treatment of precursors with M-CSF (10-100 ng/mL) resulted in increased proliferation with or without RANKL. Treatment with M-CSF (1-100 ng/mL) for 14 days caused a biphasic concentration-dependent stimulation of formation, fusion, and resorption peaking at 10-50 ng/mL and almost complete abolition of resorption at 100 ng/mL. Time-course studies using M-CSF (25 ng/mL) showed that osteoclast size, nuclei/cell, and resorption increased with longer duration of M-CSF treatment. When treatment was restricted to the first 4 days, M-CSF (25-100 ng/mL) stimulated formation of normal numbers of osteoclasts that resorbed less. Blockade of endogenous M-CSF signaling with neutralizing M-CSF antibody during the first week of culture extensively inhibited osteoclastogenesis, whereas blockade during the second week produced only a small reduction in resorption. Treatment with M-CSF during the second week of culture caused a small increase in osteoclast number and a concentration-dependent increase in cytoplasmic spreading with inhibition of resorption. We have shown that M-CSF modulates multiple steps of human osteoclastogenesis, including proliferation, differentiation and fusion of precursors. In the later stages of osteoclastogenesis, M-CSF modulates osteoclast-resorbing activity, but is not required for survival. Modulation of M-CSF signaling is a potential therapeutic target for conditions associated with excess bone resorption.

Multiple roles of M-CSF in human osteoclastogenesis. Publishing Authors By Initials

JM Hodge,MA Kirkland,GC Nicholson,JM Hodge,MA Kirkland,GC Nicholson,

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Multiple roles of M-CSF in human osteoclastogenesis. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: Journal of cellular biochemistry

VOLUME: 102

Page Numbers: 759-68

Journal Abbreviation: J. Cell. Biochem.

ISSN: 0730-2312

DAY: 15

MONTH: Oct

YEAR: 2007

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LANGUAGE: eng

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AFFILIATION: The Department of Clinical and Biomedical Sciences: Barwon Health, The University of Melbourne, Geelong, Victoria 3220, Australia. jasonh@barwonhealth.org.au

Country: United States

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MEDLINETA: J Cell Biochem

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