Preclinical validation of TGFβ inhibitors as a novel therapeutic strategy for post-traumatic heterotopic ossification.

ABSTRACT: Heterotopic ossification (HO) is characterized by the abnormal growth of ectopic bone in non-skeletal soft tissues through a fibrotic pathway and is a frequent complication in a wide variety of musculoskeletal injuries. We have previously demonstrated that TGFβ levels are elevated in the soft tissues following extremity injuries. Since TGFβ mediates the initial inflammatory and wound-healing response in the traumatized muscle bed, we hypothesized that targeted inhibition of the TGFβ pathway may be able to abrogate the unbalanced fibrotic phenotype and bone-forming response observed in post-traumatic HO. Primary mesenchymal progenitor cells (MPCs) harvested from debrided traumatized human muscle tissue were used in this study. After treatment with TGFβ inhibitors (SB431542, Galunisertib/LY2

SUBMITTER: de Vasconcellos JF 

PROVIDER: S-EPMC12022333 | biostudies-literature | 2025 Apr

REPOSITORIES: biostudies-literature