M-CSF stimulates bone resorbing activity of mature human osteoclasts via increased activation of AP-1 and NF kappa B

Hodge, J. M., Kirkland, M. A. and Nicholson, G. C. (2007). M-CSF stimulates bone resorbing activity of mature human osteoclasts via increased activation of AP-1 and NF kappa B. In: 29th Annual Meeting of the American Society for Bone and Mineral Research, Honolulu, HI, United States, (S250-S250). 16-19 September 2007. doi:10.1002/jbmr.5650221406


Author Hodge, J. M.
Kirkland, M. A.
Nicholson, G. C.
Title of paper M-CSF stimulates bone resorbing activity of mature human osteoclasts via increased activation of AP-1 and NF kappa B
Conference name 29th Annual Meeting of the American Society for Bone and Mineral Research
Conference location Honolulu, HI, United States
Conference dates 16-19 September 2007
Journal name Journal of Bone and Mineral Research   Check publisher's open access policy
Place of Publication Malden, MA United States
Publisher Wiley-Blackwell
Publication Year 2007
Sub-type Published abstract
DOI 10.1002/jbmr.5650221406
ISSN 0884-0431
1523-4681
Volume 22
Start page S250
End page S250
Total pages 1
Language eng
Abstract/Summary The critical role of M-CSF in the differentiation of osteoclasts (OC) is well established. In mature OC, M-CSF has been reported to regulate survival and motility, but no clear role in resorptive function has been established. In this study we investigated the role of M-CSF on resorbing activity of mature human OC. Human OC were generated by treatment of CFU-GM-derived precursors with soluble hRANKL (125ng/mL) and hM-CSF (25ng/mL) for 14–21d. To quantify resorbing activity, mature OC were dissociated from the plastic substrate using a non-enzymatic buffer, settled onto dentine slices and cultured for 72h. Activation of NFκB and AP-1 was assessed using a sandwich ELISA technique. IκBα and ERK were assessed by Western analysis. Neither M-CSF nor RANKL were required for mature OC survival over 72h. However, resorption function was absolutely dependent on the addition of RANKL. Co-treatment with M-CSF had a concentration-dependent biphasic action, greatly augmenting RANKL-induced resorbing activity (+181%) and actin ring formation (+131%) at 25ng/mL. RANKL alone activated NFκB (+554%). M-CSF had no effect on NFκB but potentiated RANKL-induced activation (+42%). In contrast, RANKL alone had no effect on AP-1 activation whereas M-CSF stimulated weakly (+63%) and the combination produced a synergistic effect (+171%). M-CSF activated phosphorylation of ERK 1/2, peaking at 5 min, whereas RANKL had no effect alone or in combination with M-CSF. M-CSF had no effect on IκBα phosphorylation whereas RANKL alone stimulated, with no additional effect in combination with M-CSF. Time-lapse video-microscopy showed no apparent effect of M-CSF on the motility of OC co-treated with RANKL. We have demonstrated that M-CSF is not required for survival of mature human OC, but it does potently modulate RANKL-induced resorbing activity via NFκB and AP-1 activation. The molecular mechanism of this effect remains to be determined although we propose a convergence of RANK and fms signaling (“cross-talk”) upstream of the critical OC transcription factors NFκB and AP-1. These findings have important implications for the clinical management of diseases associated with excess bone resorption.
Q-Index Code EX
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Conference Paper
Collection: School of Medicine Publications
 
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