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NOTCH signaling in skeletal progenitors is critical for fracture repair.

Publication ,  Journal Article
Wang, C; Inzana, JA; Mirando, AJ; Ren, Y; Liu, Z; Shen, J; O'Keefe, RJ; Awad, HA; Hilton, MJ
Published in: J Clin Invest
April 1, 2016

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.

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Published In

J Clin Invest

DOI

EISSN

1558-8238

Publication Date

April 1, 2016

Volume

126

Issue

4

Start / End Page

1471 / 1481

Location

United States

Related Subject Headings

  • Stromal Cells
  • Stem Cells
  • Signal Transduction
  • Receptors, Notch
  • Mice, Transgenic
  • Mice
  • Immunology
  • Fractures, Bone
  • Fracture Healing
  • Bone Marrow Cells
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Wang, C., Inzana, J. A., Mirando, A. J., Ren, Y., Liu, Z., Shen, J., … Hilton, M. J. (2016). NOTCH signaling in skeletal progenitors is critical for fracture repair. J Clin Invest, 126(4), 1471–1481. https://doi.org/10.1172/JCI80672
Wang, Cuicui, Jason A. Inzana, Anthony J. Mirando, Yinshi Ren, Zhaoyang Liu, Jie Shen, Regis J. O’Keefe, Hani A. Awad, and Matthew J. Hilton. “NOTCH signaling in skeletal progenitors is critical for fracture repair.J Clin Invest 126, no. 4 (April 1, 2016): 1471–81. https://doi.org/10.1172/JCI80672.
Wang C, Inzana JA, Mirando AJ, Ren Y, Liu Z, Shen J, et al. NOTCH signaling in skeletal progenitors is critical for fracture repair. J Clin Invest. 2016 Apr 1;126(4):1471–81.
Wang, Cuicui, et al. “NOTCH signaling in skeletal progenitors is critical for fracture repair.J Clin Invest, vol. 126, no. 4, Apr. 2016, pp. 1471–81. Pubmed, doi:10.1172/JCI80672.
Wang C, Inzana JA, Mirando AJ, Ren Y, Liu Z, Shen J, O’Keefe RJ, Awad HA, Hilton MJ. NOTCH signaling in skeletal progenitors is critical for fracture repair. J Clin Invest. 2016 Apr 1;126(4):1471–1481.

Published In

J Clin Invest

DOI

EISSN

1558-8238

Publication Date

April 1, 2016

Volume

126

Issue

4

Start / End Page

1471 / 1481

Location

United States

Related Subject Headings

  • Stromal Cells
  • Stem Cells
  • Signal Transduction
  • Receptors, Notch
  • Mice, Transgenic
  • Mice
  • Immunology
  • Fractures, Bone
  • Fracture Healing
  • Bone Marrow Cells