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Expansion of Bone Precursors through Jun as a Novel Treatment for Osteoporosis-Associated Fractures.
Expansion of Bone Precursors through Jun as a Novel Treatment for Osteoporosis-Associated Fractures. Stem cell reports Lerbs, T., Cui, L., Muscat, C., Saleem, A., van Neste, C., Domizi, P., Chan, C., Wernig, G. 2020Abstract
Osteoporosis and osteoporotic fractures lead to decreased life quality and high healthcare costs. Current treatments prevent losses in bone mass and fractures to some extent but have side effects. Therefore, better therapies are needed. This study investigated whether the transcriptionfactor Jun has a specific pro-osteogenic potency and whether modulating Jun could serve as a novel treatment for osteoporosis-associated fractures. We demonstrate that ectopically transplanted whole bones and distinct osteoprogenitors increase bone formation. Perinatal Jun induction disturbs growth plate architecture, causing a striking phenotype with shortened and thickened bones. Molecularly, Jun induces hedgehog signaling in skeletal stem cells. Therapeutically, Jun accelerates bone growth and healing in a drilling-defect model. Altogether, these results demonstrate that Jun drives bone formation by expanding osteoprogenitor populations and forcing them into the bone fate, providing a rationale for future clinical applications.
View details for DOI 10.1016/j.stemcr.2020.02.009
View details for PubMedID 32197115