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PDGF Receptor Signaling in Osteoblast Lineage Cells Controls Bone Resorption Through Upregulation of Csf1 Expression
Author(s) -
Brun Julia,
Andreasen Christina Møller,
Ejersted Charlotte,
Andersen Thomas Levin,
Caverzasio Joseph,
Thouverey Cyril
Publication year - 2020
Publication title -
journal of bone and mineral research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.882
H-Index - 241
eISSN - 1523-4681
pISSN - 0884-0431
DOI - 10.1002/jbmr.4150
Subject(s) - osteoblast , bone resorption , bone remodeling , osteoclast , endocrinology , microbiology and biotechnology , medicine , biology , resorption , chemistry , receptor , biochemistry , in vitro
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).