title: Glucocorticoid receptor antagonist and siRNA prevent senescence of human bone marrow mesenchymal stromal cells in vitro.
abstract: We investigate the effects mediated by glucocorticoid (GC) receptor (GR) blockage by using RU486, a GR antagonist and GR short interfering RNA (GR siRNA) on the proliferative and differentiation capabilities of human bone marrow mesenchymal stromal/stem cells (MSCs) and on their senescence and antioxidant levels during extended in vitro culture. Treatment with either RU486 or GR siRNA for a 7-day period significantly increased the proliferation of MSCs and their osteogenic capabilities, as reflected by an increase in alkaline phosphatase (ALP) levels after differentiation. Following 4 weeks of treatment, MSCs improved or maintained their proliferation rates, whereas control MSCs exhibited decreased proliferation. Although all MSCs exhibited reduced osteogenic potential after 4 weeks of in vitro culture, the MSCs treated with GR inhibitors showed higher ALP levels than untreated MSCs on being subjected to osteogenic differentiation. Such treatment also significantly down-regulated the adipogenic capabilities of MSCs. Telomere lengths and the activities of telomerase and superoxide dismutase of MSCs treated with either RU486 or GR siRNA appeared to be higher than those detected in controls. These results demonstrate that the blockage of effects mediated by the GCs normally found in fetal bovine serum might postpone senescence of these cells by up-regulating their antioxidant levels. Our data suggest that the blocking of the effects mediated by GCs might extend the lifespan of endogenous MSCs in patients who have elevated GC levels as a consequence of advancing age or estrogen depletion.
authors: Dows Institute for Dental Research, College of Dentistry, University of Iowa, 405N, DSB, 801 Newton Ave, Iowa City, IA, 52242, USA.
authors: Na
authors: N
authors: Wei
authors: Yang
authors: Y
authors: Yu
authors: Vijaya
authors: V
authors: Joshi
authors: Thomas
authors: T
authors: Schmidt
authors: Fang
authors: F
authors: Qian
authors: Aliasger K
authors: AK
authors: Salem
authors: Clark
authors: C
authors: Stanford
authors: Liu
authors: L
authors: Hong
mesh_terms: D000328:Adult; D001854:Bone Marrow Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D016922:Cellular Senescence / Q000187:drug effects*; D005260:Female; D006801:Humans; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D015735:Mifepristone / Q000494:pharmacology; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics; D011965:Receptors, Glucocorticoid / Q000037:antagonists & inhibitors* / Q000235:genetics* / Q000378:metabolism; D055815:Young Adult
chemical_list: D034741:RNA, Small Interfering; D011965:Receptors, Glucocorticoid; D015735:Mifepristone
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