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. 2025 Dec;61(10):1288-1299.
doi: 10.1007/s11626-025-01112-4. Epub 2025 Oct 17.

Cadmium-induced nucleus pulposus derived mesenchymal stem cells apoptosis via MAPK signaling pathway contributes to IVD degeneration

Man Hu #  1 , Yu Zhang #  2 , Wen-Jie Zhao #  3 , Xin Liu  2 , Yan-Feng Zhang  1 , Da-Xu Liu  1 , Xin-Min Feng  2 , Liang Zhang  4   5
Affiliations

Cadmium-induced nucleus pulposus derived mesenchymal stem cells apoptosis via MAPK signaling pathway contributes to IVD degeneration

Man Hu et al. In Vitro Cell Dev Biol Anim. 2025 Dec.

Abstract

The current study aimed to explore the effect of Cadmium (Cd) on nucleus pulposus derived mesenchymal stem cells (NPMSCs) and the possible mechanism of IVDD caused by Cd. In this study, cell viability assay, EdU assay, TUNEL staining, flow cytometry assay, mRNA transcriptome sequencing, quantitative real-time polymerase chain reaction (PCR) assay, immunofluorescence assay and western blot assay were used to prove that Cadmium induces apoptosis of NPMSCs. Cd impaired the proliferation of NPMSCs and promoted cell apoptosis, and this effect was time and concentration dependent. Further study also found that the expression levels of senescence-related molecules (P16, P21 and P53) in the Cd group were up-regulated and the expression levels of pro-apoptotic molecules Bax and Caspase-3 in the Cd group were significantly up-regulated, while the expression level of anti-apoptotic molecule Bcl-2 was significantly down-regulated compared with those of the Control group. The MAPK signaling pathway-related proteins were detected, and the results found that the ratios of p-P38/P38 and p-JNK/JNK in the Cd group were significantly increased, while the ratios of p-ERK/ERK was significantly less compared with the control group, and it was in a concentration-dependent relationship. Cd can inhibit the activity and proliferation of NPMSCs in a dose and time-dependent manner, and promote cell aging and apoptosis. Cd may promote the apoptosis of NPMSCs by activating MAPK signaling pathway.

Keywords: Apoptosis; Cadmium; Intervertebral disc degeneration; MAPK signaling pathway; Nucleus pulposus derived mesenchymal stem cell; Prevention.

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Conflict of interest statement

Declarations. All the procedures performed in this study were approved by the Ethical Committee of the Clinical Medical College of Yangzhou University (SBYY2020-023), Yangzhou, China. Conflict of interest: The authors declare that no conflict of interest exists. All the authors are agreed and approved the final manuscript for publication.

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