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

Area of Science:

• Bone Biology
• Cell Signaling
• Endocrinology

Background:

• The roles of platelet-derived growth factor receptors (PDGFRs) alpha and beta in osteoblast function and bone metabolism are not fully understood.
• PDGFRA and PDGFRB genes are expressed in osteoblast-lineage cells adjacent to osteoclasts in human bone remodeling units.

Purpose of the Study:

• To investigate the function of PDGFRs in osteoblast-lineage cells regarding bone metabolism.
• To determine the signaling pathways through which PDGFRs influence bone remodeling.

Main Methods:

• Utilized mouse models with genetic suppression of PDGFRs in Osterix-positive osteoblast-lineage cells.
• Analyzed trabecular bone volume, bone formation, and bone resorption markers.
• Assessed gene and protein expression, including Csf1 and M-CSF.
• Performed co-culture experiments to study osteoclastogenesis and signaling pathways (ERK1/2).

Main Results:

• Suppression of both PDGFRs in osteoblast lineage cells significantly increased trabecular bone volume in male and female mice.
• PDGFR suppression reduced osteoclast numbers and bone resorption without affecting bone formation.
• PDGFR signaling blockade inhibited PDGF-induced Csf1 expression and M-CSF secretion in osteoblasts.
• PDGFR signaling abrogation in osteoblasts impaired calcitriol-mediated osteoclastogenesis in co-cultures.

Conclusions:

• PDGFR signaling in osteoblast lineage cells is a key regulator of bone resorption.
• This regulation occurs via the ERK1/2-mediated control of Csf1 expression and subsequent M-CSF secretion.
• Targeting PDGFR signaling may offer therapeutic strategies for bone metabolic disorders characterized by excessive bone resorption.