Biochimica et Biophysica Acta (BBA) - Molecular Cell Research, Год журнала: 2025, Номер unknown, С. 119933 - 119933
Опубликована: Март 1, 2025
Язык: Английский
World Neurosurgery, Год журнала: 2025, Номер 196, С. 123732 - 123732
Опубликована: Март 13, 2025
Язык: Английский
Процитировано
0
International Journal of Nanomedicine, Год журнала: 2025, Номер Volume 20, С. 2163 - 2179
Опубликована: Фев. 1, 2025
To investigate the role of macrophage-derived small extracellular vesicles (MΦ-sEVs) in nucleus pulposus (NP) cell (NPC) senescence and screen pro-senescent micro-RNA (miRNA) MΦ-sEVs potential mRNA targets. Bone marrow-derived macrophage (BMDM)-derived sEVs were isolated by differential centrifugation, phenotypes identified. NPCs treated with MΦ-sEVs, cellular levels examined senescence-associated β-galactosidase (SA‑β‑Gal) staining Western blotting (WB). Activation secretory phenotype (SASP) was tested using qRT-PCR cytometric bead arrays (CBA). LPS+IFNγ-MΦ-sEVs or IL-4-MΦ-sEVs injected into rat coccygeal NP tissues to determine vivo effects on intervertebral disc degeneration (IVDD) NPC senescence. The miRNA evaluated PANDORA sequencing. transfected mimics inhibitors miRNAs pro-senescence effects. displayed cup-shaped morphology, diameters mainly ranging from 40 200 nm. Both impaired viability accelerated expression SASP senescence-related proteins, including p16, p21, p53, elevated treatment. Animal experiments indicated that exacerbated IVDD increased p16-positive ratio activated SASP. sequencing revealed high let-7i-5p, which exerted downregulating LIN28A expression. Inhibiting silencing C1632 specific siRNAs also triggered induced delivering let-7i-5p inhibit LIN28A.
Язык: Английский
Процитировано
0
JOR Spine, Год журнала: 2025, Номер 8(1)
Опубликована: Март 1, 2025
Intervertebral disc degeneration involves aging and senescence of nucleus pulposus cells (NPCs), JAK/STAT signaling may contribute to this process. The aim study was investigate the therapeutic effect JAK2 inhibitor, ruxolitinib, on NPC senescence. Control (third passage), Senescence (sixth JAK inhibitor (ruxolitinib-treated), siRNA-NC (control siRNA-treated), siRNA-JAK2 (JAK2-targeting siRNA-treated) groups rat NPCs were established. Cell ratios determined by β-galactosidase staining Edu conducted assess cell proliferation. cycle apoptosis analyzed flow cytometry Aggrecan Col II expression detected immunofluorescence staining. Levels IL-1β, IL-6, TNF-α, MMP-3, MMP-13 ELISA, p16, p21, p53, p-p53, JAK2, STAT3, p-JAK2, p-STAT3, ADAMTS4, ADAMTS5 levels examined western blot. More in group than group, while proliferation lower, ratio higher, percentage G0/G1 phase higher. senescence-related proteins, including higher as those MMP-13, ADAMTS5. Further, lower STAT3 (JAK2/STAT3 pathway) Ruxolitinib reversed changes described above varying degrees, results supported experiments involving targeted silencing JAK2. is characterized low proliferation, a high ratio, arrest, generation senescence-associated secretory phenotypes. can be delayed inhibiting JAK2/STAT3 using ruxolitinib.
Язык: Английский
Процитировано
0
JOR Spine, Год журнала: 2025, Номер 8(1)
Опубликована: Март 1, 2025
Intervertebral disc degeneration (IVDD) is a complex age-related physiological process, with cellular senescence (CS) being primary contributing factor. However, the precise role of CS and its associated genes in IVDD remains unclear. In this study, we performed differential expression analysis on GSE124272 GSE150408 datasets from GEO database identified 53 differentially expressed senescence-related (CSRGs). We then conducted Gene Ontology (GO) Kyoto Encyclopedia Genes Genomes (KEGG) pathway enrichment analyses to explore their functions pathways. hub by constructing protein-protein interaction (PPI) network further validated these using clinical samples. explored functional prognostic significance support vector machine recursive feature elimination (SVM-RFE), random forest (RF), least absolute shrinkage selection operator (LASSO) algorithms. visualized correlation between levels four core immune cell infiltration heat maps histograms. Finally, graphene oxide 297 (DEGs) investigate IVDD. ultimately CSRGs DUSP3, MAPKAPK5, SP1, VEGFA, various algorithms Our results revealed that DUSP3 SP1 were upregulated IVDD, while MAPKAPK5 VEGFA downregulated. Immune demonstrated positively correlated levels, whereas negatively correlated. summary, play an important pathogenesis our study gene cluster may guide future therapeutic strategies for
Язык: Английский
Процитировано
0
Biochimica et Biophysica Acta (BBA) - Molecular Cell Research, Год журнала: 2025, Номер unknown, С. 119933 - 119933
Опубликована: Март 1, 2025
Язык: Английский
Процитировано
0