Expansion of Bone Precursors through Jun as a Novel Treatment for Osteoporosis-Associated Fractures

Summary 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 transcription factor 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.
Graphical Abstract
Highlights • Jun drives the formation of bone at the expense of cartilage and stroma • Jun disturbs the proper differentiation of the developing growth plate • Jun stimulates hedgehog signaling in skeletal stem cells • Jun accelerates fracture healing in a drilling-defect model
Wernig and colleagues demonstrate the striking potency of the transcription factor Jun to expand bone precursors, drive bone formation, and accelerate fracture healing. Boosting the regenerative potential of dormant bone precursor cells, they show the potential of stem cell therapy for widespread degenerative disease.