PDGFR in PDGF-BB/PDGFR Signaling Pathway Does Orchestrates Osteogenesis in a Temporal Manner

Abstract

Platelet-derived growth factor-BB (PDGF-BB)/platelet-derived growth factor receptor-β (PDGFR-β) pathway is conventionally considered as an important pathway to promote osteogenesis; however, recent study suggested its role during osteogenesis to be controversial. Regarding the differential functions of this pathway during 3 stages of bone healing, we hypothesized that temporal inhibition of PDGF-BB/PDGFR-β pathway could shift the proliferation/differentiation balance of skeletal stem and progenitor cells, toward osteogenic lineage, which leads to improved bone regeneration. We first validated that inhibition of PDGFR-β at late stage of osteogenic induction effectively enhanced differentiation toward osteoblasts. This effect was also replicated in vivo by showing accelerated bone formation when block PDGFR-β pathway at late stage of critical bone defect healing mediated using biomaterials. Further, we found that such PDGFR-β inhibitor-initiated bone healing was also effective in the absence of scaffold implantation when administrated intraperitoneally. Mechanistically, timely inhibition of PDGFR-β blocked extracellular regulated protein kinase 1/2 pathway, which shift proliferation/differentiation balance of skeletal stem and progenitor cell to osteogenic lineage by upregulating osteogenesis-related products of Smad to induce osteogenesis. This study offered updated understanding of the use of PDGFR-β pathway and provides new insight routes of action and novel therapeutic methods in the field of bone repair.

PRP coating on different modified surfaces promoting the osteointegration of polyetheretherketone implant

“…PRP is enriched with various growth factors, including VEGF, TGF, and PDGF. Previous studies have shown that these growth factors promote osteocyte proliferation (Wu et al, 2016;Hu and Olsen, 2017;Wang et al, 2023). Therefore, in the CCK-8 test, cell proliferation on the surface of the samples in each group incubated with PRP was significantly higher than that in the non-incubated group.…”

“…Although PDGF is a recombinant growth factor approved by the FDA for clinical use to promote bone regeneration, recent studies have shown that PDGF-BB alone does not significantly directly promote bone defect repair (Luvizuto et al, 2016;de Oliveira et al, 2017;Bai et al, 2020). However, studies have shown that PDGF-BB contributes to osteocyte proliferation and intraosseous angiogenesis (Wang et al, 2023). Studies have shown that TGF-β can promote the proliferation, chemotaxis, and early differentiation of osteoprogenitor cells through the Smad pathway and inhibit osteoclast differentiation by downregulating the RANKL/OPG secretion ratio (Wu et al, 2016).…”

Exploring causal correlations between inflammatory cytokines and ankylosing spondylitis: a bidirectional mendelian-randomization study

“…PDGF-BB)/PDGFR-β pathway is generally considered an important pathway for promoting bone formation. PDGF-BB, as a growth factor derived from platelets, is regarded as a key factor in the pathological bone formation of AS ( 47 , 48 ). The relationship between IFN-γ and AS has been extensively studied.…”

Spatiotemporal multi-omics: exploring molecular landscapes in aging and regenerative medicine

“…The processes governing regeneration predominantly encompass cell proliferation, migration, differentiation, and the precise patterning of regenerating tissues and organs [ 218 , 219 ]. Cell proliferation serves as the foundational process, where new tissues or organs arise through cellular division and propagation [ 220 – 223 ]. Cell migration involves the movement of cells from one location to another, establishing the correct structural arrangement [ 221 , 224 , 225 ].…”