PDGF Receptor Signaling in Osteoblast Lineage Cells Controls Bone Resorption Through Upregulation of Csf1 Expression.
Julia BrunChristina Møller AndreasenCharlotte EjerstedThomas Levin AndersenJoseph CaverzasioCyril ThouvereyPublished in: Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research (2020)
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).
Keyphrases
- bone loss
- bone regeneration
- bone mineral density
- induced apoptosis
- poor prognosis
- cell cycle arrest
- growth factor
- signaling pathway
- soft tissue
- postmenopausal women
- endoplasmic reticulum stress
- cell death
- oxidative stress
- binding protein
- cell proliferation
- mesenchymal stem cells
- endothelial cells
- cerebrospinal fluid
- transcription factor
- dna methylation
- lps induced
- cell fate
- high glucose
- insulin resistance
- diabetic rats