Validation of a Novel Model of Recurrent Heteropic Ossification
Shawn Loder, BS, Shailesh Agarwal, MD, David Cholok, BS, Christopher Breuler, BS, James Drake, BS, Stewart Wang, MD, PhD, Benjamin Levi, MD.
University of Michigan, Ann Arbor, MI, USA.
PURPOSE: Current treatment strategies for heterotopic ossification (HO) include surgical extirpation. However, excision rarely alleviates the long-term sequelae of HO such as chronic pain and open wounds and these patients often suffer from recurrence. Here we describe a new model of recurrent HO which re-expresses the signaling mediators present during initial HO formation.
METHODS: Wild-type C57BL/6 mice underwent 30% TBSA burn with Achilles’ tenotomy to induce HO at the tenotomy site. After 9 weeks, mice underwent baseline microCT followed by HO excision and immediate re-imaging within 72 hours. Mice were allowed to survive an additional 9 weeks, at which time repeat imaging was performed. Immunostaining for pSMAD1/5, a known mediator of BMP signaling, was performed in a subset euthanized 3 weeks after excision.
RESULTS: By microCT, we identified the presence of new ossified lesions occurring post-excision (A). Alcian blue and Immunostaining of samples 3 weeks after initial burn/tenotomy showed substantial cartilage and pSMAD 1/5 expression. However 9 weeks after initial burn/tenotomy, cartilage and pSMAD1/5 were almost eliminated. In post-excisional HO, recurrence of new cartilage and pSMAD1/5 expression was noted by 3 weeks (B).
CONCLUSION: We have designed a model of recurrent HO following surgical excision. Similar signaling mediators as during initial HO were up-regulated, including pSMAD 1/5. Patients who undergo HO excision may benefit from therapeutics which are currently being evaluated to prevent initial HO.
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