| First Author | Lin YM | Year | 2016 |
| Journal | Biochem Biophys Res Commun | Volume | 469 |
| Issue | 4 | Pages | 903-10 |
| PubMed ID | 26721440 | Mgi Jnum | J:233160 |
| Mgi Id | MGI:5780903 | Doi | 10.1016/j.bbrc.2015.12.003 |
| Citation | Lin YM, et al. (2016) Target disruption of ribosomal protein pNO40 accelerates aging and impairs osteogenic differentiation of mesenchymal stem cells. Biochem Biophys Res Commun 469(4):903-10 |
| abstractText | 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 ( big up tri, openE2), exon 4 ( big up tri, openE4) or big up tri, openE2+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, big up tri, openE4 null embryos exhibited prominent senescence-associated beta-galactosidase (SA-beta-gal) staining, a marker for senescent cells, in notochord, forelimbs and heart while bone marrow-derived mesenchymal stem cells (MSCs) from big up tri, openE4 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 big up tri, openE4 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. |
