What this means
Researchers grew disc cells in a dish with an inflammation signal. Boosting NEDD4 eased aging and cell death, and it broke down another protein called PTEN. More tests in living animals and more checks are still needed.
Plain-English summary written by an AI model from the abstract. The original is below.
- Who it was tested in
- Two types of human disc cells grown in a lab dish
- Kind of research
- A study
The science
- Original title
- Neural precursor cell expressed developmentally downregulated 4-mediated phosphatase and tensin homolog ubiquitination alleviates senescence and apoptosis of nucleus pulposus cells under interleukin-1 beta conditions.
- Authors
- Lin Y, Li C, Chang X et al.
- Journal
- The Journal of international medical research
- Published
- Oct 27, 2026
- Study type
- Study · in humans
- PMID
- 42946644 ↗
Abstract
ObjectiveIncreasing evidence indicates that aging and apoptosis of nucleus pulposus cells are closely associated with the pathogenesis of intervertebral disc degeneration. This study investigated the role of E3 ubiquitin ligase neural precursor cell expressed developmentally downregulated gene 4 (NEDD4) in the interleukin-1 beta-induced aging and apoptosis of human nucleus pulposus cells and evaluated whether NEDD4 mediates these effects by promoting the ubiquitination and degradation of phosphatase and tensin homolog (PTEN).MethodsTwo commercially available immortalized human nucleus pulposus cells were used for in vitro experiments, without involving human participants or collecting human tissues. The cells were treated with interleukin-1 beta (10 ng/mL for 24 h) to establish an inflammatory model of intervertebral disc degeneration. Transfection of overexpressed NEDD4 and/or PTEN was performed in the model cells. Cell viability, apoptosis, senescence, oxidative stress, inflammatory mediators, and extracellular matrix-related proteins were assessed. The interactions between NEDD4 and PTEN and the stability of the PTEN protein were investigated using co-immunoprecipitation, actinomycin D tracking, MG132 treatment, and intracellular ubiquitination experiments.ResultsInterleukin-1 beta treatment downregulated NEDD4 expression in nucleus pulposus cells to 2.3-fold of the baseline level (p < 0.001) while simultaneously upregulated PTEN protein expression to 1.8-fold of the baseline level (p < 0.01). Overexpression of NEDD4 shortened the half-life of PTEN protein from 8 h to 3 h through the ubiquitin-proteasome-dependent degradation pathway (p < 0.001). In addition, overexpression of NEDD4 reduced the level of reactive oxygen species, inhibited cell apoptosis, decreased the expression levels of p21 and p16, and restored the expression levels of type II collagen and aggrecan (p < 0.05). NEDD4 interacted with PTEN and enhanced its ubiquitination. Functional rescue experiments indicated that overexpression of PTEN weakened the protective effects of NEDD4.ConclusionsThis study preliminarily demonstrated that the overexpression of NEDD4 can alleviate the interleukin-1 beta-induced apoptosis and senescence phenomena of nucleus pulposus cells. This effect may be partially mediated by promoting the ubiquitination of PTEN and the proteasome degradation pathway. However, further functional deficiency experiments and in vivo validations are warranted to establish the causal relationship and therapeutic relevance.
Lin Y, Li C, Chang X et al. Neural precursor cell expressed developmentally downregulated 4-mediated phosphatase and tensin homolog ubiquitination alleviates senescence and apoptosis of nucleus pulposus cells under interleukin-1 beta conditions. The Journal of international medical research. 2026. doi:10.1177/03000605261499771. PMID: 42946644. https://pubmed.ncbi.nlm.nih.gov/42946644/
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