direct-mouse-traumaburn-model-of-heterotopic-ossification

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 ...

University of Michigan Medical School

Heterotopic ossification (HO) is a common and debilitating complication of burns, traumatic brain injuries, and musculoskeletal trauma and surgery. Although the exact mechanism of ectopic bone formation is unknown, mesenchymal stem cells (MSCs) capable of osteogenic differentiation are known to play an essential role. Interestingly, the prevalence of HO in the elderly population is low despite the high overall occurrence of musculoskeletal injury and orthopedic procedures. We hypothesized that a lower osteogenicity of MSCs would be associated with blunted HO formation in old compared with young mice. In vitro osteogenic differentiation of adipose-derived MSCs from old (18-20 months) and young (6-8 weeks) C57/BL6 mice was assessed, with or without preceding burn injury. In vivo studies were then performed using an Achilles tenotomy with concurrent burn injury HO model. HO formation was quantified using μCT scans, Raman spectroscopy, and histology. MSCs from young mice had more in vitro bone formation, upregulation of bone formation pathways, and higher activation of Smad and nuclear factor kappa B (NF-κB) signaling following burn injury. This effect was absent or blunted in cells from old mice. In young mice, burn injury significantly increased HO formation, NF-κB activation, and osteoclast activity at the tenotomy site. This blunted, reactive osteogenic response in old mice follows trends seen clinically and may be related to differences in the ability to mount acute inflammatory responses. This unique characterization of HO and MSC osteogenic differentiation following inflammatory insult establishes differences between age populations and suggests potential pathways that could be targeted in the future with therapeutics.

Effects of aging on osteogenic response and heterotopic ossification following burn injury in mice.

The component separation technique (CST) is an important technique now used frequently in complex ventral hernia repair (VHR). Although this technique has demonstrated superior success rates, there is a paucity of research describing how release of the external obliques coupled with rectus myofascial advancement alters the morphology of the abdominal architecture. In this study, we apply the new concept of analytic morphomics to describe the immediate changes in morphology of the abdomen that take place after VHR by CST.

Article	Year
Effects of aging on osteogenic response and heterotopic ossification following burn injury in mice. Stem cells and development\| PubMed ID: 25122460	2015
Abdominal wall dynamics after component separation hernia repair. The Journal of surgical research\| PubMed ID: 25201576	2015

R. Cameron Brownley

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