Target disruption of ribosomal protein pNO40 accelerates aging and impairs osteogenic differentiation of mesenchymal stem cells

Yen Ming Lin, Chih Ching Wu, Yu Chen Chang, Chu Han Wu, Hsien Li Ho, Ji Wei Hu, Ren Chi Chang, Chung Ta Wang, Pin Ouyang*

*Corresponding author for this work

Research output: Contribution to journalJournal Article peer-review

6 Scopus citations

Abstract

pNO40/PS1D, a novel nucleolar protein, has been characterized as a core protein of eukaryotic 60S ribosome and at least two splicing forms of pNO40 mRNAs with alternative starting sites have been identified. Through production of knockout (ko) mice with either exon 2 (▵E2), exon 4 (▵E4) or ▵E2+E4 targeted disruption we identified a cryptic splicing product occurring in the ko tissues examined which in general cannot be observed in regular RT-PCR detection of wild-type (wt) animals. Among ko animals, ▵E4 null embryos exhibited prominent senescence-associated β-galactosidase (SA-β-gal) staining, a marker for senescent cells, in notochord, forelimbs and heart while bone marrow-derived mesenchymal stem cells (MSCs) from ▵E4 null mice developed accelerated aging and osteogenic differentiation defects compared to those from wt and other isoform mutant mice. Examination of the causal relationship between pNO40 deficiency and MSC-accelerated aging revealed ▵E4 null disruption in MSCs elicits high levels of ROS and elevated expression levels of p16 and Rb but not p53. Further analysis with iTraq identified CYP1B1, a component of the cytochrome p450 system, as a potential molecule mediating ROS generation in pNO40 deficient MSCs. We herein established a mouse model of MSC aging through pNO40-targeted depletion and demonstrated the effects of loss of pNO40 on bone homeostasis.

Original languageEnglish
Pages (from-to)903-910
Number of pages8
JournalBiochemical and Biophysical Research Communications
Volume469
Issue number4
DOIs
StatePublished - 22 01 2016

Bibliographical note

Publisher Copyright:
© 2015 Elsevier Inc. All rights reserved.

Keywords

  • Aging
  • Knockout mice
  • Mesenchymal stem cells
  • Osteogenesis
  • pNO40

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