PDGF Receptor Signaling in Osteoblast Lineage Cells Controls Bone Resorption Through Upregulation of Csf1 Expression

Julia Brun, Christina Møller Andreasen, Charlotte Ejersted, Thomas Levin Andersen, Joseph Caverzasio, Cyril Thouverey

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Abstract

The physiological functions of platelet-derived growth factor receptors (PDGFRs) α and β in osteoblast biology and bone metabolism remain to be established. Here, we show that PDGFRA and PDGFRB genes are expressed by osteoblast-lineage canopy and reversal cells in close proximity to PDGFB-expressing osteoclasts within human trabecular bone remodeling units. We also report that, although removal of only one of the two PDGFRs in Osterix-positive cells does not affect bone phenotype, suppression of both PDGFRs in those osteoblast lineage cells increases trabecular bone volume in male mice as well as in female gonad-intact and ovariectomized mice. Furthermore, osteoblast lineage-specific suppression of PDGFRs reduces Csf1 expression, bone marrow level of macrophage colony-stimulating factor (M-CSF), number of osteoclasts, and, therefore, bone resorption, but does not change bone formation. Finally, abrogation of PDGFR signaling in osteoblasts blocks PDGF-induced ERK1/2-mediated Csf1 expression and M-CSF secretion in osteoblast cultures and calcitriol-mediated osteoclastogenesis in co-cultures. In conclusion, our results indicate that PDGFR signaling in osteoblast lineage cells controls bone resorption through ERK1/2-mediated Csf1 expression. © 2020 American Society for Bone and Mineral Research (ASBMR).

OriginalsprogEngelsk
TidsskriftJournal of Bone and Mineral Research
Vol/bind35
Udgave nummer12
Sider (fra-til)2458-2469
ISSN0884-0431
DOI
StatusUdgivet - dec. 2020

Bibliografisk note

© 2020 American Society for Bone and Mineral Research (ASBMR).

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