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Direct Mouse Trauma/Burn Model of Heterotopic Ossification.

Abstract
Heterotopic ossification (HO) is the formation of bone outside of the skeleton which forms following major trauma, burn injuries, and orthopaedic surgical procedures. The majority of animal models used to study HO rely on the application of exogenous substances, such as bone morphogenetic protein (BMP), exogenous cell constructs, or genetic mutations in BMP signaling. While these models are useful they do not accurately reproduce the inflammatory states that cause the majority of cases of HO. Here we describe a burn/tenotomy model in mice that reliably produces focused HO. This protocol involves creating a 30% total body surface area partial thickness contact burn on the dorsal skin as well as division of the Achilles tendon at its midpoint. Relying solely on traumatic injury to induce HO at a predictable location allows for time-course study of endochondral heterotopic bone formation from intrinsic physiologic processes and environment only. This method could prove instrumental in understanding the inflammatory and osteogenic pathways involved in trauma-induced HO. Furthermore, because HO develops in a predictable location and time-course in this model, it allows for research to improve early imaging strategies and treatment modalities to prevent HO formation.
AuthorsJonathan R Peterson, Shailesh Agarwal, R Cameron Brownley, Shawn J Loder, Kavitha Ranganathan, Paul S Cederna, Yuji Mishina, Stewart C Wang, Benjamin Levi
JournalJournal of visualized experiments : JoVE (J Vis Exp) Issue 102 Pg. e52880 (Aug 06 2015) ISSN: 1940-087X [Electronic] United States
PMID26274052 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Video-Audio Media)
Topics
  • Achilles Tendon (pathology, surgery)
  • Animals
  • Bone Development
  • Burns (pathology)
  • Disease Models, Animal
  • Mice
  • Mice, Inbred C57BL
  • Ossification, Heterotopic (etiology, pathology)
  • Skin (pathology)
  • Wounds and Injuries (pathology)

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