title: Defective bone repair in mast cell-deficient Cpa3Cre/+ mice.
abstract: In the adult skeleton, cells of the immune system interact with those of the skeleton during all phases of bone repair to influence the outcome. Mast cells are immune cells best known for their pathologic role in allergy, and may be involved in chronic inflammatory and fibrotic disorders. Potential roles for mast cells in tissue homeostasis, vascularization and repair remain enigmatic. Previous studies in combined mast cell- and Kit-deficient KitW-sh/W-sh mice (KitW-sh) implicated mast cells in bone repair but KitW-sh mice suffer from additional Kit-dependent hematopoietic and non- hematopoietic deficiencies that could have confounded the outcome. The goal of the current study was to compare bone repair in normal wild type (WT) and Cpa3Cre/+ mice, which lack mast cells in the absence of any other hematopoietic or non- hematopoietic deficiencies. Repair of a femoral window defect was characterized using micro CT imaging and histological analyses from the early inflammatory phase, through soft and hard callus formation, and finally the remodeling phase. The data indicate 1) mast cells appear in healing bone of WT mice but not Cpa3Cre/+ mice, beginning 14 days after surgery; 2) re-vascularization of repair tissue and deposition of mineralized bone was delayed and dis-organised in Cpa3Cre/+ mice compared with WT mice; 3) the defects in Cpa3Cre/+ mice were associated with little change in anabolic activity and biphasic alterations in osteoclast and macrophage activity. The outcome at 56 days postoperative was complete bridging of the defect in most WT mice and fibrous mal-union in most Cpa3Cre/+ mice. The results indicate that mast cells promote bone healing, possibly by recruiting vascular endothelial cells during the inflammatory phase and coordinating anabolic and catabolic activity during tissue remodeling. Taken together the data indicate that mast cells have a positive impact on bone repair.
authors.affiliation: Bone Engineering Labs, Research Institute-McGill University Health Centre. Montreal General Hospital C10.160, Cedar Ave., Montreal, QC, Canada.|Experimental Surgery, Faculty of Medicine, McGill University. Rue de la Montaigne, Montreal, QC, Canada.
authors.forename: Jose Luis
authors.identifier: http://orcid.org/0000-0002-3953-9762
authors.initials: JL
authors.lastname: Ramirez-GarciaLuna
authors.affiliation: Bone Engineering Labs, Research Institute-McGill University Health Centre. Montreal General Hospital C10.160, Cedar Ave., Montreal, QC, Canada.|Biotechnology Program, University of British Columbia, West Mall, Vancouver, BC, Canada.
authors.forename: Daniel
authors.initials: D
authors.lastname: Chan
authors.affiliation: Bone Engineering Labs, Research Institute-McGill University Health Centre. Montreal General Hospital C10.160, Cedar Ave., Montreal, QC, Canada.
authors.forename: Robert
authors.initials: R
authors.lastname: Samberg
authors.affiliation: Bone Engineering Labs, Research Institute-McGill University Health Centre. Montreal General Hospital C10.160, Cedar Ave., Montreal, QC, Canada.|Experimental Medicine, Faculty of Medicine, McGill University. Rue de la Montaigne, Montreal, QC, Canada.
authors.forename: Mira
authors.initials: M
authors.lastname: Abou-Rjeili
authors.affiliation: Bone Engineering Labs, Research Institute-McGill University Health Centre. Montreal General Hospital C10.160, Cedar Ave., Montreal, QC, Canada.|Biotechnology Program, University of British Columbia, West Mall, Vancouver, BC, Canada.
authors.forename: Timothy H
authors.initials: TH
authors.lastname: Wong
authors.affiliation: Bone Engineering Labs, Research Institute-McGill University Health Centre. Montreal General Hospital C10.160, Cedar Ave., Montreal, QC, Canada.
authors.forename: Ailian
authors.initials: A
authors.lastname: Li
authors.affiliation: Division of Cellular Immunology, German Cancer Research Center, Heidelberg, Germany.
authors.forename: Thorsten B
authors.initials: TB
authors.lastname: Feyerabend
authors.affiliation: Division of Cellular Immunology, German Cancer Research Center, Heidelberg, Germany.
authors.forename: Hans-Reimer
authors.initials: HR
authors.lastname: Rodewald
authors.affiliation: Bone Engineering Labs, Research Institute-McGill University Health Centre. Montreal General Hospital C10.160, Cedar Ave., Montreal, QC, Canada.|Experimental Surgery, Faculty of Medicine, McGill University. Rue de la Montaigne, Montreal, QC, Canada.|Experimental Medicine, Faculty of Medicine, McGill University. Rue de la Montaigne, Montreal, QC, Canada.
authors.forename: Janet E
authors.initials: JE
authors.lastname: Henderson
authors.affiliation: Bone Engineering Labs, Research Institute-McGill University Health Centre. Montreal General Hospital C10.160, Cedar Ave., Montreal, QC, Canada.|Experimental Surgery, Faculty of Medicine, McGill University. Rue de la Montaigne, Montreal, QC, Canada.
authors.forename: Paul A
authors.initials: PA
authors.lastname: Martineau
mesh_terms: D000818:Animals; D001861:Bone Regeneration; D043422:Carboxypeptidases A / Q000235:genetics*; D005260:Female; D005269:Femur / Q000098:blood supply / Q000293:injuries* / Q000473:pathology* / Q000502:physiology; D017353:Gene Deletion; D008297:Male; D008407:Mast Cells / Q000378:metabolism / Q000473:pathology*; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout
chemical_list: D043422:Carboxypeptidases A; C503326:Cpa3 protein, mouse