Heterotopic ossification (HO), characterized by the formation of mature bone in the soft tissues, is a complication that can accompany musculoskeletal injury, and it is a frequent occurrence within the military population that has experienced orthopaedic combat trauma. The etiology of this disease is largely unknown. Our laboratory has developed strategies to investigate the cellular and molecular events leading to HO using clinical specimens that were obtained during irrigation and debridement of musculoskeletal injuries. Our approach enables to study (1) the cell types that are responsible for pathological transformation and ossification, (2) the cell- and tissue-level signaling that induces the pathologic transformation, and (3) the effect of extracellular matrix topography and force transduction on HO progression. In this review, we will report on our findings in each of these aspects of HO etiology and describe our efforts to recapitulate our findings in an animal model for traumatic HO.
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