UBE2E3 regulates cellular senescence and osteogenic differentiation of BMSCs during aging.
UBE2E3 regulates cellular senescence and osteogenic differentiation of BMSCs during aging.
复制标题
UBE2E3 调节衰老过程中 BMSC 的细胞衰老和成骨分化
作者：
Liu Y;Cai G;Chen P;Jiang T;Xia Z
研究背景骨质疏松症已逐渐成为世界性的公共卫生问题。然而，骨质疏松症的确切分子机制仍不清楚。骨髓间充质干细胞（BMSCs）的衰老和成骨分化抑制在骨质疏松症中起重要作用。方法利用两个与骨质疏松症相关的基因表达谱（GSE 35956和GSE 35958），筛选有希望的基因泛素结合酶E2 E3（UBE 2E3）。然后通过体外实验验证其功能和机制。结果UBE 2E3在骨髓中高表达，与成骨相关基因表达呈正相关。UBE 2E3在老年BMSCs中的表达较年轻BMSCs减少。在体外实验中，UBE 2E3的敲低加速了细胞衰老，抑制了年轻BMSCs的成骨分化。另一方面，UBE 2E3的过表达减弱了细胞衰老，并增强了老年BMSCs的成骨分化。UBE 2E3可能通过调控核因子红细胞2相关因子（Nrf2）的功能，从而影响BMSCs的衰老和成骨分化。结论UBE 2E3可能通过调控BMSCs的衰老和成骨分化参与骨质疏松的发病机制。
Background Osteoporosis has gradually become a public health problem in the world. However, the exact molecular mechanism of osteoporosis still remains unclear. Senescence and osteogenic differentiation inhibition of bone marrow mesenchymal stem cells (BMSCs ) are supposed to play an important part in osteoporosis. Methods We used two gene expression profiles (GSE35956 and GSE35958) associated with osteoporosis and selected the promising gene Ubiquitin-conjugating enzyme E2 E3 (UBE2E3). We then verified its function and mechanism by in vitro experiments. Results UBE2E3 was highly expressed in the bone marrow and positively associated with osteogenesis related genes. Besides, UBE2E3 expression reduced in old BMSCs compared with that in young BMSCs. In in vitro experiments, knockdown of UBE2E3 accelerated cellular senescence and inhibited osteogenic differentiation of young BMSCs. On the other hand, overexpression of UBE2E3 attenuated cellular senescence as well as enhanced osteogenic differentiation of old BMSCs. Mechanistically, UBE2E3 might regulate the nuclear factor erythroid 2-related factor (Nrf2) and control its function, thus affecting the senescence and osteogenic differentiation of BMSCs. Conclusion UBE2E3 may be potentially involved in the pathogenesis of osteoporosis by regulating cellular senescence and osteogenic differentiation of BMSCs.
登录
查看更多内容
DOI：
10.1016/j.ecl.2012.04.006
发表时间：
2012-09-01
影响因子：
4.5
作者：
Armas, Laura A. G.;Recker, Robert R.
通讯作者：
Recker, Robert R.
褪黑激素通过激活 NRF2 和抑制 ER 应激来预防犬脂肪间充质干细胞的衰老
DOI：
10.18632/aging.101602
发表时间：
2018-10-25
期刊：
Aging
影响因子：
--
作者：
Fang J;Yan Y;Teng X;Wen X;Li N;Peng S;Liu W;Donadeu FX;Zhao S;Hua J
通讯作者：
Hua J
DOI：
10.1016/j.trsl.2020.06.007
发表时间：
2020-12
期刊：
Translational research : the journal of laboratory and clinical medicine
影响因子：
--
作者：
Kaur J;Farr JN
通讯作者：
Farr JN
影响因子：
4.1
作者：
Chen, Xiao;Wang, Keyue;Zhu, Guoying
通讯作者：
Zhu, Guoying
影响因子：
29
作者：
Berger, Julian Meyer;Singh, Parminder;Karsenty, Gerard
通讯作者：
Karsenty, Gerard