Exogenous hedgehog antagonist delays but does not prevent fracture healing in young mice.

ABSTRACT: Fracture healing recapitulates many aspects of developmental osteogenesis. The hedgehog (Hh) signaling pathway, essential to skeletal development, is upregulated during fracture healing, although its importance is unclear. Our goal was to assess the functional importance of Hh signaling in endochondral fracture healing. We created closed, transverse diaphyseal femur fractures in mice, stabilized with an intramedullary pin, and administered a systemic Hh inhibitor or vehicle. Because Hh pathway activation is mediated by the receptor Smoothened (Smo), we used the Smo antagonist GDC-0449 (GDC, 50mg/kg, twice daily) to target the pathway. First, in vehicle-treated 10-wk. female C57BL/6 mice we confirmed that Hh signaling was increased in fracture callus compared to intact bone, with >5-fold up

SUBMITTER: Liu X 

PROVIDER: S-EPMC5568453 | biostudies-literature | 2017 Oct

REPOSITORIES: biostudies-literature