UBE2E3 regulates cellular senescence and osteogenic differentiation of BMSCs during aging

Abstract

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.

Age Related Osteoporosis: Targeting Cellular Senescence

“…Mechanisms underlying senescent induced changes in MSCs have since then been addressed in multiple studies, identifying important mediators of MSC senescence [ 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 ]. For instance, several miRNAs have been identified that are involved in regulating senescence and the balance between osteoblastic and adipocytic differentiation of BMSCs [ 52 , 55 , 60 , 61 ].…”

“…Ubiquitin-conjugating enzyme E2E3 ( UB3E2E3 ) in vitro knock-down in young BMSCs accelerated cellular senescence and inhibited osteogenic differentiation [ 58 ]. In addition, knockdown of Bmi-1 , an important epigenetic regulator of stem cell self-renewal, leads to cellular senescence in young MSCs and overexpression to rejuvenation of old MSCs.…”

miR-143-3p Promotes Ovarian Granulosa Cell Senescence and Inhibits Estradiol Synthesis by Targeting UBE2E3 and LHCGR

“…Moreover, Mulan E3 ubiquitin ligase and UBE2E3 formed Mulan–Ube2e3 complexes, which then recruited GABARAP (GABAA receptor-associated protein) to participate in the process of mitosis [ 49 ]. Studies have found that UBE2E3 regulated cellular senescence in bone marrow mesenchymal stem cells (BMSCs) during aging and that this regulatory effect was achieved by modulating the function of the nuclear factor erythroid 2-related factor (Nrf2) [ 50 ]. Indeed, another study found that UBE2E3, together with its nuclear import receptor importin 11 (Imp-11), regulated Nrf2 distribution and activity in cells.…”

Long noncoding RNA Gm31629 promotes bone regeneration by maintaining bone marrow mesenchymal stem cells activity

“…Western blotting was performed as previously described ( Liu et al, 2021b ; Peng et al, 2019 ). Total cell proteins were separated by SDS-PAGE and blotted on PVDF membranes (Millipore, Sigma, Burlington, MA).…”