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The Damage-Associated Molecular Pattern (Damp) Hmgb1 Limits the Progression of Heterotopic Ossifaction in a Mouse Model
Fady. P Marji; Lucas Dvoracek; Kyle Parks; Jennifer Hall; Erin E. Andstadt; Gregory Cooper; Joseph E. Losee
University of Pittsburgh Medical Center
2020-02-15
Presenter: Fady P. Marji
Affidavit:
The work represents the original work of the residents involved with guidance and editing provided by associated attending faculty and laboratory director Gregory Cooper.
Director Name: Vu T. Nguyen MD
Author Category: Other Specialty Resident
Presentation Category: Basic Science Research
Abstract Category: General Reconstruction
Introduction: Heterotopic ossification (HO) is the pathological formation of bone in non-osseous tissues, and its treatment often requires large soft tissue resections with reconstruction. We attempted to non-surgically mitigate the development of HO via modulation of inflammation using local treatment with HMGB1, a damage associated molecular pattern (DAMP).
Methods: Sixteen mice were injected subcutaneously with 1 �g of rhBMP2 impregnated in 300 �L of Matrigel and maintained for four weeks as a model for the induction of HO. All animals then underwent micro computed tomography (micro-CT) imaging for the evaluation of HO formation at the injection site (treatment Day 0). Experimental animals underwent treatment with 10 �g of HMGB1 in 250 �L of phosphate buffered saline (PBS), injected subcutaneously directly at the site of palpable heterotopic bone, every other day, for a total of fourteen days. Control mice were injected with 250 �L of PBS. Micro-CT imaging was performed on days seven and fourteen. HO tissue underwent histochemical analysis. Bone volumes were compared using 3D Slicer software.
Results: Both groups continued growing bone throughout the study. Treatment with HMGB1 led to a significant lower mean volume of heterotopic bone growth compared to PBS treatment at seven (121.33% � 16.02 [Experimental] vs.145.98% � 22.37 [Control], p≤0.05) and fourteen-day (201.88% � 56.76 [Experimental] vs 253.45% � 53.23 [Control], p≤0.05). TRAP staining revealed no difference in the number of multinucleated osteoclasts
Conclusions: HMGB1 may be useful in the treatment of heterotopic ossification. Further investigations are needed to decipher its mechanism of action
