title: Defective bone repair in mast cell deficient mice with c-Kit loss of function.
abstract: KitW-sh mice carry an inactivating mutation in the gene encoding the receptor for stem cell factor, which is expressed at high levels on the surface of haematopoietic precursor cells. The mutation results in mast cell deficiency, a variety of defects in innate immunity and poorly defined abnormalities in bone. The present study was designed to characterise healing of a cortical window defect in skeletally mature KitW-sh mice using high-resolution micro computed tomographic imaging and histological analyses. The cortical bone defect healed completely in all wild type mice but failed to heal in about half of the KitW-sh mice by 12 weeks post-operative. Defective healing was associated with premature and excessive expression of TRAP positive cells embedded in fibrous marrow but with little change in ALP activity. Immuno-histochemical analyses revealed reduced CD34 positive vascular endothelial cells and F4/80 positive macrophages at 1 and 2 weeks post-operative. Impaired bone healing in the KitW-sh mice was therefore attributed to altered catabolic activity, impaired re-vascularisation and compromised replacement of woven with compact bone.
authors.affiliation: Bone Engineering Labs, Research Institute-McGill University Health Centre, Surgical Research, C9.133, Montreal General Hospital, 1650 Cedar Ave, Montreal, Quebec, H3G 1A4, Canada.janet.henderson@mcgill.ca.
authors.forename: D A
authors.initials: DA
authors.lastname: Behrends
authors.forename: L
authors.initials: L
authors.lastname: Cheng
authors.forename: M B
authors.initials: MB
authors.lastname: Sullivan
authors.forename: M H
authors.initials: MH
authors.lastname: Wang
authors.forename: G B
authors.initials: GB
authors.lastname: Roby
authors.forename: N
authors.initials: N
authors.lastname: Zayed
authors.forename: C
authors.initials: C
authors.lastname: Gao
authors.forename: J E
authors.initials: JE
authors.lastname: Henderson
authors.forename: P A
authors.initials: PA
authors.lastname: Martineau
mesh_terms: D000818:Animals; D001861:Bone Regeneration; D005269:Femur / Q000000981:diagnostic imaging / Q000502:physiology* / Q000601:surgery; D008407:Mast Cells / Q000378:metabolism* / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D009154:Mutation; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics* / Q000378:metabolism; D011859:Radiography
chemical_list: D019009:Proto-Oncogene Proteins c-kit