Direct Mouse Trauma/Burn Model of Heterotopic Ossification.
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.
Department of Surgery, University of Michigan Medical School.
Jonathan R
JR
Peterson
Department of Surgery, University of Michigan Medical School.
Shailesh
S
Agarwal
Department of Surgery, University of Michigan Medical School.
R Cameron
RC
Brownley
Department of Surgery, University of Michigan Medical School.
Shawn J
SJ
Loder
Department of Surgery, University of Michigan Medical School.
Kavitha
K
Ranganathan
Department of Surgery, University of Michigan Medical School.
Paul S
PS
Cederna
Department of Biologic and Materials Sciences, University of Michigan School of Dentistry.
Yuji
Y
Mishina
Department of Surgery, University of Michigan Medical School.
Stewart C
SC
Wang
Department of Surgery, University of Michigan Medical School; blevi@umich.edu.
Benjamin
B
Levi
D000125:Achilles Tendon / Q000473:pathology* / Q000601:surgery*; D000818:Animals; D001846:Bone Development; D002056:Burns / Q000473:pathology*; D004195:Disease Models, Animal; D051379:Mice; D008810:Mice, Inbred C57BL; D009999:Ossification, Heterotopic / Q000209:etiology / Q000473:pathology*; D012867:Skin / Q000473:pathology; D014947:Wounds and Injuries / Q000473:pathology*