title: Long-term functional engraftment of mesenchymal progenitor cells in a mouse model of accelerated aging.
abstract: Age-related osteoporosis is characterized by a decrease in bone-forming capacity mediated by defects in the number and function of osteoblasts. An important cellular mechanism that may in part explain osteoblast dysfunction that occurs with aging is senescence of mesenchymal progenitor cells (MPCs). In the telomere-based Wrn(-/-) Terc(-/-) model of accelerated aging, the osteoporotic phenotype of these mice is also associated with a major decline in MPC differentiation into osteoblasts. To investigate the role of MPC aging as a cell-autonomous mechanism in senile bone loss, transplantation of young wild-type whole bone marrow into Wrn(-/-) Terc(-/-) mutants was performed and the ability of engrafted cells to differentiate into cells of the osteoblast lineage was assessed. We found that whole bone marrow transplantation in Wrn(-/-) Terc(-/-) mice resulted in functional engraftment of MPCs up to 42 weeks, which was accompanied by a survival advantage as well as delays in microarchitectural features of skeletal aging.
authors.affiliation: Department of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
authors.forename: Lakshman
authors.initials: L
authors.lastname: Singh
authors.forename: Tracy A
authors.initials: TA
authors.lastname: Brennan
authors.forename: Jung-Hoon
authors.initials: JH
authors.lastname: Kim
authors.forename: Kevin P
authors.initials: KP
authors.lastname: Egan
authors.forename: Emily A
authors.initials: EA
authors.lastname: McMillan
authors.forename: Qijun
authors.initials: Q
authors.lastname: Chen
authors.forename: Kurt D
authors.initials: KD
authors.lastname: Hankenson
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhang
authors.forename: Stephen G
authors.initials: SG
authors.lastname: Emerson
authors.forename: F Brad
authors.initials: FB
authors.lastname: Johnson
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Pignolo
mesh_terms: D000375:Aging / Q000473:pathology*; D000818:Animals; D002454:Cell Differentiation / Q000502:physiology; D016922:Cellular Senescence / Q000502:physiology; D004195:Disease Models, Animal; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D051379:Mice; D008822:Mice, Transgenic; D010024:Osteoporosis / Q000473:pathology*; D016019:Survival Analysis; D016615:Telomere / Q000473:pathology