title: Fracture healing in protease-activated receptor-2 deficient mice.
abstract: 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.
authors.affiliation: Department of Orthopaedics, Vanderbilt University Medical Center, Nashville, Tennessee 37232-9565, USA.
authors.forename: Kevin R
authors.initials: KR
authors.lastname: O'Neill
authors.forename: Christopher M
authors.initials: CM
authors.lastname: Stutz
authors.forename: Nicholas A
authors.initials: NA
authors.lastname: Mignemi
authors.forename: Heather
authors.initials: H
authors.lastname: Cole
authors.forename: Matthew R
authors.initials: MR
authors.lastname: Murry
authors.forename: Jeffry S
authors.initials: JS
authors.lastname: Nyman
authors.forename: Heidi
authors.initials: H
authors.lastname: Hamm
authors.forename: Jonathan G
authors.initials: JG
authors.lastname: Schoenecker
mesh_terms: D000818:Animals; D001696:Biomechanical Phenomena / Q000502:physiology; D002146:Bony Callus / Q000473:pathology; D005260:Female; D005264:Femoral Fractures / Q000000981:diagnostic imaging / Q000473:pathology*; D017102:Fracture Healing / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D044464:Receptor, PAR-2 / Q000172:deficiency* / Q000502:physiology; D014057:Tomography, X-Ray Computed
chemical_list: D044464:Receptor, PAR-2