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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 µg of rhBMP2 impregnated in 300 µL 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 µg of HMGB1 in 250 µL 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 µL 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
