PDGF inhibits BMP2-induced bone healing

Abstract

Bone regeneration depends on a pool of bone/cartilage stem/progenitor cells and signaling mechanisms regulating their differentiation. Using in vitro approach, we have shown that PDGF signaling through PDGFRβ inhibits BMP2-induced osteogenesis, and significantly attenuates expression of BMP2 target genes. We evaluated outcomes of treatment with two anabolic agents, PDGF and BMP2 using different bone healing models. Targeted deletion of PDGFRβ in αSMA osteoprogenitors, led to increased callus bone mass, resulting in improved biomechanical properties of fractures. In critical size bone defects BMP2 treatment increased proportion of osteoprogenitors, while the combined treatment of PDGF BB with BMP2 decreased progenitor number at the injury site. BMP2 treatment induced significant bone formation and increased number of osteoblasts, while in contrast combined treatment with PDGF BB decreased osteoblast numbers. This is in vivo study showing that PDGF inhibits BMP2-induced osteogenesis, but inhibiting PDGF signaling early in healing process does not improve BMP2-induced bone healing.

Recombinant Human Peptide Growth Factors, Bone Morphogenetic Protein-7 (rhBMP7), and Platelet-Derived Growth Factor-BB (rhPDGF-BB) for Osteoporosis Treatment in an Oophorectomized Rat Model

“…They also observed antagonistic effects between the signaling of these two proteins when administered simultaneously [ 69 ]. Another study by Novak et al (2023) showed that the combination of these two growth factors compromises the bone healing model, with PDGF-BB inhibiting BMP-2-induced osteogenesis [ 70 ]. This effect could be associated with PDGF-BB’s inhibition of the BMP2/Smad canonical signaling pathway [ 61 ].…”

Endothelial to mesenchymal Notch signaling regulates skeletal repair

“…Interestingly, we did not observe significant deletion of Dll4 in Cdh5CreER/DllD female mice. We previously reported lower efficiency of Cre recombination in female animals using the aSMA promoter (22,23,48). Sex differences and/or decreased targeted gene expression in females could lead to inefficient Cre recombination (23).…”

“…Critical size femoral defects. C57Bl/6J animals aged 3.5-7 months were used to evaluate critical size femoral healing (2 mm) using an established protocol and commercially available external fixation (MouseExFix, RISystem) (48). DLL4 (5 µg, R&D Systems, USA), JAG1 (6 µg, R&D Systems, USA), or their combination with BMP2 (5 µg) was applied on an adsorbable collagen sponge as a scaffold (Medtronic, USA) cut to size (3 × 4 × 4 mm) onto which growth factors were loaded in a 7 µl volume.…”

“…Two sections per sample were collected from the middle of a fracture or bone sample after critical size defects, stained, and scanned using an Axioscan 7 microscope (Zeiss, Germany). For automated cell counting, we used ImageJ (NIH, USA) as previously published (48).…”

The Role of XBP1 in bone metabolism

“…BMP2 is a highly conserved functional protein of the TGF-β family, promoting osteogenesis ( 52 , 53 ). It was shown by immunofluorescence that XBP1 highly expresses in human periodontal ligament cells (hPDLCs).…”