Tendon-derived stem/progenitor cell aging: defective self-renewal and altered fate.
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.
Zhou
Zuping
Z
Department of Orthopaedics, Mount Sinai School of Medicine, New York, NY, USA.
Akinbiyi
Takintope
T
Xu
Lili
L
Ramcharan
Melissa
M
Leong
Daniel J
DJ
Ros
Stephen J
SJ
Colvin
Alexis C
AC
Schaffler
Mitchell B
MB
Majeska
Robert J
RJ
Flatow
Evan L
EL
Sun
Hui B
HB
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
D015415:Biomarkers; C517260:CITED2 protein, rat; D018960:Hyaluronan Receptors; D014157:Transcription Factors