Innovating intervertebral disc degeneration therapy: Harnessing the power of extracellular vesicles

Journal of Orthopaedic Translation, Год журнала: 2025, Номер 50, С. 44 - 55

Опубликована: Янв. 1, 2025

Язык: Английский

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Reprogramming to restore youthful epigenetics of senescent nucleus pulposus cells for mitigating intervertebral disc degeneration and alleviating low back pain

Bone Research, Год журнала: 2025, Номер 13(1)

Опубликована: Март 12, 2025

Abstract Aging is a pivotal risk factor for intervertebral disc degeneration (IVDD) and chronic low back pain (LBP). The restoration of aging nucleus pulposus cells (NPCs) to youthful epigenetic state crucial IVDD treatment, but remains formidable challenge. Here, we proposed strategy partially reprogram reinstate epigenetics senescent NPCs by delivering plasmid carrier that expressed pluripotency-associated genes ( Oct4 , Klf4 Sox2 ) in Cavin2-modified exosomes (OKS@M-Exo) treatment alleviating LBP. functional OKS@M-Exo efficaciously alleviated senescence markers p16 INK4a p21 CIP1 p53 ), reduced DNA damage H4K20me3 expression, as well restored proliferation ability metabolic balance NPCs, validated through vitro experiments. In rat model IVDD, maintained height, hydration tissue structure, effectively ameliorated via decreasing the markers. Additionally, nociceptive behavior downregulated nociception markers, indicating its efficiency transcriptome sequencing analysis also demonstrated could decrease expression age-related pathways restore cell proliferation. Collectively, reprogramming may hold promise therapeutic platform treat IVDD.

Язык: Английский

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BRD4/MAP2K7/PGF Signaling Axis Promotes Senescence and Extracellular Matrix Metabolism of Nucleus Pulposus Cells in Intervertebral Disk Degeneration

Aging Cell, Год журнала: 2025, Номер unknown

Опубликована: Март 25, 2025

Intervertebral disk degeneration (IDD) is a common age-related degenerative disease of the spine that imposes substantial economic burden on both families and society. Despite advances in understanding mechanisms underlying IDD, effective therapeutic interventions for its treatment prevention remain elusive. Our previous study identified positive correlation between IDD severity bromodomain-containing protein 4 (BRD4) expression. However, multifaceted role BRD4 still not fully understood. This explored abnormal elevation expression nucleus pulposus (NP) tissues from patients with an rat model IDD. We found levels were positively correlated NP senescence extracellular matrix (ECM) degradation inversely ECM anabolism. These relationships further confirmed through assays measuring senescence-associated β-galactosidase activity, markers P21 P16, secretory phenotype indicators (IL-6, IL-8, MMP3, MMP13), as well metabolism such collagen II aggrecan. Mechanistically, aberrant was to upregulate MAP2K7, which turn enhances PGF expression, promoting cell metabolism. findings highlight crucial BRD4/MAP2K7/PGF signaling axis cellular regulation, suggesting represents promising target

Язык: Английский

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A dual-targeted trinity of antibody-peptide-drug delivery consortium to combat HER2+ tumor

Chemical Communications, Год журнала: 2024, Номер 60(93), С. 13742 - 13745

Опубликована: Янв. 1, 2024

We report for the first time that an anticancer drug–peptide conjugate containing γEγE in its side chain and RGD motif exhibits high affinity Herceptin facilitates self-assembly to form antibody–peptide–drug nanofibers.

Язык: Английский

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