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

Tristan Lerbs, Lu Cui, Claire Muscat, Atif Saleem, Camille van Neste, Pablo Domizi, Charles Chan, Gerlinde Wernig

Research output: Contribution to journalArticlepeer-review

14 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)603-613
Number of pages11
JournalStem Cell Reports
Volume14
Issue number4
DOIs
StatePublished - 14 Apr 2020
Externally publishedYes

Keywords

  • JUN
  • bone precursor expansion
  • bone precursors
  • fractures
  • osteoporosis
  • osteoprogenitors
  • skeletal stem cells
  • stem cell therapy

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