Fracture healing in protease-activated receptor-2 deficient mice

Protease-activated receptor-2 (PAR-2) provides an important link between extracellular proteases and the cellular initiation of inflammatory responses. The effect of PAR-2 on fracture healing is unknown. This study investigates the in vivo effect of PAR-2 deletion on fracture healing by assessing differences between wild-type (PAR-2 ^+/+) and knock-out (PAR-2 ^-/-) mice. Unilateral mid-shaft femur fractures were created in 34 PAR-2 ^+/+ and 28 PAR-2 ^-/- mice after intramedullary fixation. Histologic assessments were made at 1, 2, and 4 weeks post-fracture (wpf), and radiographic (plain radiographs, micro-computed tomography (μCT)) and biomechanical (torsion testing) assessments were made at 7 and 10 wpf. Both the fractured and un-fractured contralateral femur specimens were evaluated. Polar moment of inertia (pMOI), tissue mineral density (TMD), bone volume fraction (BV/TV) were determined from μCT images, and callus diameter was determined from plain radiographs. Statistically significant differences in callus morphology as assessed by μCT were found between PAR-2 ^-/- and PAR-2 ^+/+ mice at both 7 and 10 wpf. However, no significant histologic, plain radiographic, or biomechanical differences were found between the genotypes. The loss of PAR-2 was found to alter callus morphology as assessed by μCT but was not found to otherwise effect fracture healing in young mice.