Multiple roles of M-CSF in human osteoclastogenesis

Hodge, Jason M., Kirkland, Mark A. and Nicholson, Geoffrey C. (2007) Multiple roles of M-CSF in human osteoclastogenesis. Journal of Cellular Biochemistry, 102 3: 759-768. doi:10.1002/jcb.21331


Author Hodge, Jason M.
Kirkland, Mark A.
Nicholson, Geoffrey C.
Title Multiple roles of M-CSF in human osteoclastogenesis
Journal name Journal of Cellular Biochemistry   Check publisher's open access policy
ISSN 0730-2312
1097-4644
Publication date 2007-10
Sub-type Article (original research)
DOI 10.1002/jcb.21331
Volume 102
Issue 3
Start page 759
End page 768
Total pages 10
Place of publication Hoboken, NJ, United States
Publisher John Wiley & Sons
Language eng
Abstract 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.
Keyword M-CSF
Osteoclastogenesis
CFU-GM
Proliferation
Differentiation
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: School of Medicine Publications
 
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