title: Tendon-derived stem/progenitor cell aging: defective self-renewal and altered fate.
abstract: Aging is a major risk factor for tendon injury and impaired tendon healing, but the basis for these relationships remains poorly understood. Here we show that rat tendon- derived stem ⁄ progenitor cells (TSPCs) differ in both self-renewal and differentiation capability with age. The frequency of TSPCs in tendon tissues of aged animals is markedly reduced based on colony formation assays. Proliferation rate is decreased, cell cycle progression is delayed and cell fate patterns are also altered in aged TSPCs. In particular, expression of tendon lineage marker genes is reduced while adipocytic differentiation increased. Cited2, a multi-stimuli responsive transactivator involved in cell growth and senescence, is also downregulated in aged TSPCs while CD44, a matrix assembling and organizing protein implicated in tendon healing, is upregulated, suggesting that these genes participate in the control of TSPC function.
authors.affiliation: Department of Orthopaedics, Mount Sinai School of Medicine, New York, NY, USA.
authors.forename: Zuping
authors.initials: Z
authors.lastname: Zhou
authors.forename: Takintope
authors.initials: T
authors.lastname: Akinbiyi
authors.forename: Lili
authors.initials: L
authors.lastname: Xu
authors.forename: Melissa
authors.initials: M
authors.lastname: Ramcharan
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Leong
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Ros
authors.forename: Alexis C
authors.initials: AC
authors.lastname: Colvin
authors.forename: Mitchell B
authors.initials: MB
authors.lastname: Schaffler
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Majeska
authors.forename: Evan L
authors.initials: EL
authors.lastname: Flatow
authors.forename: Hui B
authors.initials: HB
authors.lastname: Sun
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D002453:Cell Cycle; D002454:Cell Differentiation; D019070:Cell Lineage; D049109:Cell Proliferation; D016922:Cellular Senescence / Q000502:physiology*; D018960:Hyaluronan Receptors / Q000378:metabolism; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D012038:Regeneration; D013234:Stem Cells / Q000166:cytology* / Q000502:physiology*; D013710:Tendons / Q000166:cytology*; D014157:Transcription Factors / Q000378:metabolism
chemical_list: D015415:Biomarkers; C517260:CITED2 protein, rat; D018960:Hyaluronan Receptors; D014157:Transcription Factors