Pdgfreceptor Signaling In Osteoblast Lineage Cells Controls Bone Resorption Through Upregulation Ofcsf1expression

The physiological functions of platelet-derived growth factor receptors (PDGFRs) alpha and beta in osteoblast biology and bone metabolism remain to be established. Here, we show thatPDGFRAandPDGFRBgenes are expressed by osteoblast-lineage canopy and reversal cells in close proximity toPDGFB-expressing osteoclasts within human trabecular bone remodeling units. We also report that, although removal of only one of the two PDGFRs inOsterix-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 reducesCsf1expression, 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-mediatedCsf1expression 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-mediatedCsf1expression. (c) 2020 American Society for Bone and Mineral Research (ASBMR).