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bioRxiv · 10.1101/2023.11.04.565143

Post-translational regulation of Platelet-derived growth factor receptor β is critical for fracture repair in aged mice

Tao, J.·Lipe, B.·Boyce, B.·Xing, L.·ZHANG, H.
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Abstract

Increased protein ubiquitination was observed in fracture callus and particularly in aged mice. Treatment of proteasome inhibitor enhanced fracture repair in young and mice by increasing the number of mesenchymal progenitor cells (MPCs). However, the protein targets of proteasome inhibitor are still not known. Ub-proteomics identifies the top ub-proteins in MPCs and osteoblasts. Among them, PDGFR{beta} plays important roles both in osteogenesis and angiogenesis, which were reduced in callus of aged mice. We examine the dramatic decrease of PDGFR{beta} protein level, increased Ub-PDGFR{beta}, but mild decrease of mRNA in callus of aged mice, suggesting dys-regulated protein modification is the major cause of decreased PDGFR{beta} level. Decreased PDGFR{beta} results in the failure of PDGF-BB enhanced MPCs proliferation and fracture repair in aged mice. Co-treatment with proteasome inhibitor rescues the ability of PDGF-BB on MPC proliferation and fracture repair. Our findings not only discover the protein target of proteasome inhibitor in MPCs, but importantly connect the compromised effect of PDGF treatment on diseases with PDGFR{beta} proteasomal degradation. We open a new avenue for the treatment of fracture repair in elderly with the combination of PDGF-BB and proteasome inhibitor.

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Tao, J., Lipe, B., Boyce, B., Xing, L., ZHANG, H.. 2023-11-05. Post-translational regulation of Platelet-derived growth factor receptor β is critical for fracture repair in aged mice. https://doi.org/10.1101/2023.11.04.565143

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