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M-csf potently augments rankl-induced resorption activation in mature human osteoclasts

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journal contribution
posted on 2024-06-17, 19:13 authored by JM Hodge, Fiona CollierFiona Collier, NJ Pavlos, MA Kirkland, GC Nicholson
Macrophage-CSF (M-CSF) is critical for osteoclast (OC) differentiation and is reported to enhance mature OC survival and motility. However, its role in the regulation of bone resorption, the main function of OCs, has not been well characterised. To address this we analysed short-term cultures of fully differentiated OCs derived from human colony forming unit-granulocyte macrophages (CFU-GM). When cultured on dentine, OC survival was enhanced by M-CSF but more effectively by receptor activator of NFκB ligand (RANKL). Resorption was entirely dependent on the presence of RANKL. Co-treatment with M-CSF augmented RANKL-induced resorption in a concentration-dependent manner with a (200-300%) stimulation at 25 ng/mL, an effect observed within 4-6 h. M-CSF co-treatment also increased number of resorption pits and F-actin sealing zones, but not the number of OCs or pit size, indicating stimulation of the proportion of OCs activated. M-CSF facilitated RANKL-induced activation of c-fos and extracellular signal-regulated kinase (ERK) 1/2 phosphorylation, but not NFκB nor nuclear factor of activated T-cells, cytoplasmic-1 (NFATc1). The mitogen-activated protein kinase kinase (MEK) 1 inhibitor PD98059 partially blocked augmentation of resorption by M-CSF. Our results reveal a previously unidentified role of M-CSF as a potent stimulator of mature OC resorbing activity, possibly mediated via ERK upstream of c-fos.

History

Journal

PLoS ONE

Volume

6

Article number

ARTN e21462

Location

United States

Open access

  • Yes

ISSN

1932-6203

eISSN

1932-6203

Language

English

Publication classification

C1.1 Refereed article in a scholarly journal

Copyright notice

2011, Hodge et al

Issue

6

Publisher

PUBLIC LIBRARY SCIENCE