title: Exposure to a youthful circulaton rejuvenates bone repair through modulation of β-catenin.
abstract: The capacity for tissues to repair and regenerate diminishes with age. We sought to determine the age-dependent contribution of native mesenchymal cells and circulating factors on in vivo bone repair. Here we show that exposure to youthful circulation by heterochronic parabiosis reverses the aged fracture repair phenotype and the diminished osteoblastic differentiation capacity of old animals. This rejuvenation effect is recapitulated by engraftment of young haematopoietic cells into old animals. During rejuvenation, β-catenin signalling, a pathway important in osteoblast differentiation, is modulated in the early repair process and required for rejuvenation of the aged phenotype. Temporal reduction of β-catenin signalling during early fracture repair improves bone healing in old mice. Our data indicate that young haematopoietic cells have the capacity to rejuvenate bone repair and this is mediated at least in part through β-catenin, raising the possibility that agents that modulate β-catenin can improve the pace or quality of fracture repair in the ageing population.
authors.affiliation: Department of Developmental and Stem Cell Biology, Hospital for Sick Children, University of Toronto, Toronto, Ontario M5G 0A4, Canada.
authors.forename: Gurpreet S
authors.initials: GS
authors.lastname: Baht
authors.affiliation: Department of Developmental and Stem Cell Biology, Hospital for Sick Children, University of Toronto, Toronto, Ontario M5G 0A4, Canada.
authors.forename: David
authors.initials: D
authors.lastname: Silkstone
authors.affiliation: Department of Developmental and Stem Cell Biology, Hospital for Sick Children, University of Toronto, Toronto, Ontario M5G 0A4, Canada.
authors.forename: Linda
authors.initials: L
authors.lastname: Vi
authors.affiliation: Department of Developmental and Stem Cell Biology, Hospital for Sick Children, University of Toronto, Toronto, Ontario M5G 0A4, Canada.
authors.forename: Puviindran
authors.initials: P
authors.lastname: Nadesan
authors.affiliation: Department of Developmental and Stem Cell Biology, Hospital for Sick Children, University of Toronto, Toronto, Ontario M5G 0A4, Canada.
authors.forename: Yasha
authors.initials: Y
authors.lastname: Amani
authors.affiliation: Department of Developmental and Stem Cell Biology, Hospital for Sick Children, University of Toronto, Toronto, Ontario M5G 0A4, Canada.
authors.forename: Heather
authors.initials: H
authors.lastname: Whetstone
authors.affiliation: Department of Developmental and Stem Cell Biology, Hospital for Sick Children, University of Toronto, Toronto, Ontario M5G 0A4, Canada.
authors.forename: Qingxia
authors.initials: Q
authors.lastname: Wei
authors.affiliation: Department of Developmental and Stem Cell Biology, Hospital for Sick Children, University of Toronto, Toronto, Ontario M5G 0A4, Canada.|Department of Orthopedics, Duke University, Durham, North Carolina 27710, USA.
authors.forename: Benjamin A
authors.initials: BA
authors.lastname: Alman
mesh_terms: D000483:Alleles; D000818:Animals; D001665:Binding Sites; D001853:Bone Marrow / Q000473:pathology; D001842:Bone and Bones / Q000473:pathology; D002454:Cell Differentiation; D017077:Culture Media, Conditioned; D005260:Female; D005452:Fluoresceins / Q000737:chemistry; D017102:Fracture Healing; D050723:Fractures, Bone / Q000473:pathology; D006412:Hematopoietic Stem Cells / Q000166:cytology; D059630:Mesenchymal Stem Cells / Q000166:cytology; D051379:Mice; D008822:Mice, Transgenic; D010006:Osteoblasts / Q000166:cytology / Q000378:metabolism; D010012:Osteogenesis; D010227:Parabiosis; D010641:Phenotype; D012038:Regeneration; D015398:Signal Transduction; D013977:Tibia / Q000473:pathology; D013997:Time Factors; D051153:Wnt Proteins / Q000378:metabolism; D051176:beta Catenin / Q000378:metabolism*
chemical_list: C495267:CTNNB1 protein, mouse; D017077:Culture Media, Conditioned; D005452:Fluoresceins; D051153:Wnt Proteins; D051176:beta Catenin; C007740:fluorexon