Abstract 2: Macrophage-specific TGF-B is a Targetable Cytokine to Prevent Heterotopic Ossification

PURPOSE: Transforming growth factor beta (TGFβ) signaling is central to both normal and pathologic wound healing. However the source of TGFβ ligand during wound healing remains unknown. Heterotopic ossification (HO) is the pathologic formation of endochondral bone in soft tissue commonly occurring after severe trauma. HO is a SMAD-signaling dependent process typically occurring in response to an acute inflammatory insult. Traditionally targeted therapeutics for treatment of HO have focused on mesenchymal cell progenitors. However, macrophages which are integral orchestrators of the initial inflammatory response and are primary agents of cytokine secretion in wound regeneration, have received little attention. Here we identify a role of macrophage production of TGFβ in HO and demonstrate a role for macrophage targeted therapies in the treatment and prevention of this debilitating condition