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Vitamin C Treatment Rescues Prelamin A-Induced Premature Senescence of Subchondral Bone Mesenchymal Stem Cells.
Qu, Yan-Nv; Zhang, Li; Wang, Ting; Zhang, He-Yang; Yang, Ze-Ji; Yuan, Fang-Fang; Wang, Yan; Li, Si-Wei; Jiang, Xiao-Xia; Xie, Xiao-Hua.
Afiliación
  • Qu YN; Chinese PLA General Hospital, 28 Fuxing Road, Haidian District, Beijing 100853, China.
  • Zhang L; Department of Neural Engineering and Biological Interdisciplinary Studies, Institute of Military Cognition and Brain Sciences, Academy of Military Medical Sciences, 27 Taiping Road, Haidian District, Beijing 100850, China.
  • Wang T; Department of Neural Engineering and Biological Interdisciplinary Studies, Institute of Military Cognition and Brain Sciences, Academy of Military Medical Sciences, 27 Taiping Road, Haidian District, Beijing 100850, China.
  • Zhang HY; Department of Neural Engineering and Biological Interdisciplinary Studies, Institute of Military Cognition and Brain Sciences, Academy of Military Medical Sciences, 27 Taiping Road, Haidian District, Beijing 100850, China.
  • Yang ZJ; Department of Neural Engineering and Biological Interdisciplinary Studies, Institute of Military Cognition and Brain Sciences, Academy of Military Medical Sciences, 27 Taiping Road, Haidian District, Beijing 100850, China.
  • Yuan FF; Department of Neural Engineering and Biological Interdisciplinary Studies, Institute of Military Cognition and Brain Sciences, Academy of Military Medical Sciences, 27 Taiping Road, Haidian District, Beijing 100850, China.
  • Wang Y; Department of Neural Engineering and Biological Interdisciplinary Studies, Institute of Military Cognition and Brain Sciences, Academy of Military Medical Sciences, 27 Taiping Road, Haidian District, Beijing 100850, China.
  • Li SW; Department of Neural Engineering and Biological Interdisciplinary Studies, Institute of Military Cognition and Brain Sciences, Academy of Military Medical Sciences, 27 Taiping Road, Haidian District, Beijing 100850, China.
  • Jiang XX; Department of Neural Engineering and Biological Interdisciplinary Studies, Institute of Military Cognition and Brain Sciences, Academy of Military Medical Sciences, 27 Taiping Road, Haidian District, Beijing 100850, China.
  • Xie XH; Chinese PLA General Hospital, 28 Fuxing Road, Haidian District, Beijing 100853, China.
Stem Cells Int ; 2020: 3150716, 2020.
Article en En | MEDLINE | ID: mdl-32322277
Aging is a predominant risk factor for many chronic conditions. Stem cell dysfunction plays a pivotal role in the aging process. Prelamin A, an abnormal processed form of the nuclear lamina protein lamin A, has been reported to trigger premature senescence. However, the mechanism driving stem cell dysfunction is still unclear. In this study, we found that while passaging subchondral bone mesenchymal stem cells (SCB-MSCs) in vitro, prelamin A accumulation occurred concomitantly with an increase in senescence-associated ß-galactosidase (SA-ß-Gal) expression. Unlike their counterparts, SCB-MSCs with prelamin A overexpression (MSC/PLA) demonstrated decreased proliferation, osteogenesis, and adipogenesis but increased production of inflammatory factors. In a hind-limb ischemia model, MSC/PLA also exhibited compromised therapy effect. Further investigation showed that exogenous prelamin A triggered abnormal nuclear morphology, DNA and shelterin complex damage, cell cycle retardation, and eventually cell senescence. Changes in gene expression profile were also verified by microarray assay. Interestingly, we found that ascorbic acid or vitamin C (VC) treatment could inhibit prelamin A expression in MSC/PLA and partially reverse the premature aging in MSC/PLA, with reduced secretion of inflammatory factors and cell cycle arrest and resistance to apoptosis. Importantly, after VC treatment, MSC/PLA showed enhanced therapy effect in the hind-limb ischemia model. In conclusion, prelamin A can accelerate SCB-MSC premature senescence by inducing DNA damage. VC can be a potential therapeutic reagent for prelamin A-induced aging defects in MSCs.

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Tipo de estudio: Prognostic_studies / Risk_factors_studies Idioma: En Revista: Stem Cells Int Año: 2020 Tipo del documento: Article País de afiliación: China Pais de publicación: Estados Unidos

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Tipo de estudio: Prognostic_studies / Risk_factors_studies Idioma: En Revista: Stem Cells Int Año: 2020 Tipo del documento: Article País de afiliación: China Pais de publicación: Estados Unidos