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Direct Mouse Trauma/Burn Model of Heterotopic Ossification
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Osteoblasts Have a Neural Origin in Heterotopic Ossification.

ZaWaunyka W Lazard1, Elizabeth A Olmsted-Davis, Elizabeth A Salisbury

  • 1Department of Pediatrics, Center for Cell and Gene Therapy, Baylor College of Medicine, One Baylor Plaza, Houston, TX, 77030, USA.

Clinical Orthopaedics and Related Research
|May 7, 2015
PubMed
Summary

Osteogenic progenitors in sensory nerves drive heterotopic ossification (HO). These cells, originating in the endoneurium, travel via blood vessels to form new bone at non-skeletal sites, revealing a neurological basis for HO.

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Area of Science:

  • Cell Biology
  • Neuroscience
  • Orthopedics

Background:

  • Heterotopic ossification (HO) involves bone formation in non-skeletal tissues.
  • Previous research indicated sensory nerves play a role in early HO.
  • This study identifies specific osteogenic progenitor cells within sensory nerve endoneurium.

Purpose of the Study:

  • Characterize the nature of osteoprogenitors in peripheral nerve endoneurium.
  • Investigate the mechanism of osteoprogenitor migration from nerves to sites of new bone formation.

Main Methods:

  • Induced HO in mice using bone morphogenetic protein-2 (BMP-2).
  • Utilized immunohistochemistry, fluorescence-activated cell sorting, and immunocytochemistry to identify and characterize osteoprogenitors.
  • Employed quantitative reverse transcription-polymerase chain reaction to track cell marker expression and extravasation kinetics.

Main Results:

  • Osteoblast-specific transcription factors appeared in endoneurial cells within 24 hours of HO induction.
  • These cells expressed neural and endothelial markers (PDGFRα, musashi-1, p75NTR, Tie-2) and claudin 5.
  • Endoneurial osteoprogenitors migrated via blood vessels, extravasated into the HO site, and expressed osteoblast markers.

Conclusions:

  • Endoneurial progenitors are the primary osteogenic precursors in HO.
  • These cells exit nerves, travel through circulation, and extravasate to form new bone.
  • HO involves a unique osteoblast biogenesis, suggesting a neurological component and potential shifts in orthopedic treatment strategies.