Rib Fractures and Death from Deletion of Osteoblast βcatenin in Adult Mice Is Rescued by Corticosteroids

Jin Zhu Duan, Yueh Lee, Corey Jania, Jucheng Gong, Mauricio Rojas, Laurel Burk, Monte Willis, Jonathon Homeister, Stephen Tilley, Janet Rubin, Arjun Deb

Research output: Contribution to journalArticle

2 Scopus citations

Abstract

Ribs are primarily made of cortical bone and are necessary for chest expansion and ventilation. Rib fractures represent the most common type of non-traumatic fractures in the elderly yet few studies have focused on the biology of rib fragility. Here, we show that deletion of βcatenin in Col1a2 expressing osteoblasts of adult mice leads to aggressive osteoclastogenesis with increased serum levels of the osteoclastogenic cytokine RANKL, extensive rib resorption, multiple spontaneous rib fractures and chest wall deformities. Within days of osteoblast specific βcatenin deletion, animals die from respiratory failure with a vanishing rib cage that is unable to sustain ventilation. Increased bone resorption is also observed in the vertebrae and femur. Treatment with the bisphosphonate pamidronate delayed but did not prevent death or associated rib fractures. In contrast, administration of the glucocorticoid dexamethasone decreased serum RANKL and slowed osteoclastogenesis. Dexamethasone preserved rib structure, prevented respiratory compromise and strikingly increased survival. Our findings provide a novel model of accelerated osteoclastogenesis, where deletion of osteoblast βcatenin in adults leads to rapid development of destructive rib fractures. We demonstrate the role of βcatenin dependent mechanisms in rib fractures and suggest that glucocorticoids, by suppressing RANKL, may have a role in treating bone loss due to aggressive osteoclastogenesis.

Original languageEnglish (US)
Article numbere55757
JournalPloS one
Volume8
Issue number2
DOIs
StatePublished - Feb 5 2013

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

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    Duan, J. Z., Lee, Y., Jania, C., Gong, J., Rojas, M., Burk, L., Willis, M., Homeister, J., Tilley, S., Rubin, J., & Deb, A. (2013). Rib Fractures and Death from Deletion of Osteoblast βcatenin in Adult Mice Is Rescued by Corticosteroids. PloS one, 8(2), [e55757]. https://doi.org/10.1371/journal.pone.0055757