NOTCH signaling in skeletal progenitors is critical for fracture repair.

Journal Article (Journal Article)

Fracture nonunions develop in 10%-20% of patients with fractures, resulting in prolonged disability. Current data suggest that bone union during fracture repair is achieved via proliferation and differentiation of skeletal progenitors within periosteal and soft tissues surrounding bone, while bone marrow stromal/stem cells (BMSCs) and other skeletal progenitors may also contribute. The NOTCH signaling pathway is a critical maintenance factor for BMSCs during skeletal development, although the precise role for NOTCH and the requisite nature of BMSCs following fracture is unknown. Here, we evaluated whether NOTCH and/or BMSCs are required for fracture repair by performing nonstabilized and stabilized fractures on NOTCH-deficient mice with targeted deletion of RBPjk in skeletal progenitors, maturing osteoblasts, and committed chondrocytes. We determined that removal of NOTCH signaling in BMSCs and subsequent depletion of this population result in fracture nonunion, as the fracture repair process was normal in animals harboring either osteoblast- or chondrocyte-specific deletion of RBPjk. Together, this work provides a genetic model of a fracture nonunion and demonstrates the requirement for NOTCH and BMSCs in fracture repair, irrespective of fracture stability and vascularity.

Full Text

Duke Authors

Cited Authors

  • Wang, C; Inzana, JA; Mirando, AJ; Ren, Y; Liu, Z; Shen, J; O'Keefe, RJ; Awad, HA; Hilton, MJ

Published Date

  • April 1, 2016

Published In

Volume / Issue

  • 126 / 4

Start / End Page

  • 1471 - 1481

PubMed ID

  • 26950423

Pubmed Central ID

  • PMC4811137

Electronic International Standard Serial Number (EISSN)

  • 1558-8238

Digital Object Identifier (DOI)

  • 10.1172/JCI80672


  • eng

Conference Location

  • United States