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1,25(OH)(2)D(3) Mitigates Oxidative Stress-Induced Damage to Nucleus Pulposus-Derived Mesenchymal Stem Cells through PI3K/Akt Pathway

Intervertebral disc degeneration (IVDD) is one of the main causes of low back pain. The local environment of the degenerated intervertebral disc (IVD) increases oxidative stress and apoptosis of endogenous nucleus pulposus-derived mesenchymal stem cells (NPMSCs) and weakens its ability of endogenous...

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Autores principales: Wang, Jun-wu, Zhu, Lei, Shi, Peng-zhi, Wang, Ping-chuan, Dai, Yan, Wang, Yong-xiang, Lu, Xu-hua, Cheng, Xiao-fei, Feng, Xin-min, Zhang, Liang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Hindawi 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8956384/
https://www.ncbi.nlm.nih.gov/pubmed/35340208
http://dx.doi.org/10.1155/2022/1427110
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author Wang, Jun-wu
Zhu, Lei
Shi, Peng-zhi
Wang, Ping-chuan
Dai, Yan
Wang, Yong-xiang
Lu, Xu-hua
Cheng, Xiao-fei
Feng, Xin-min
Zhang, Liang
author_facet Wang, Jun-wu
Zhu, Lei
Shi, Peng-zhi
Wang, Ping-chuan
Dai, Yan
Wang, Yong-xiang
Lu, Xu-hua
Cheng, Xiao-fei
Feng, Xin-min
Zhang, Liang
author_sort Wang, Jun-wu
collection PubMed
description Intervertebral disc degeneration (IVDD) is one of the main causes of low back pain. The local environment of the degenerated intervertebral disc (IVD) increases oxidative stress and apoptosis of endogenous nucleus pulposus-derived mesenchymal stem cells (NPMSCs) and weakens its ability of endogenous repair ability in degenerated IVDs. A suitable concentration of 1α,25-dihydroxyvitamin D(3) (1,25(OH)(2)D(3)) has been certified to reduce oxidative stress and cell apoptosis. The current study investigated the protective effect and potential mechanism of 1,25(OH)(2)D(3) against oxidative stress-induced damage to NPMSCs. The present results showed that 1,25(OH)(2)D(3) showed a significant protective effect on NPMSCs at a concentration of 10(−10) M for 24 h. Protective effects of 1,25(OH)(2)D(3) were also exhibited against H(2)O(2)-induced NPMSC senescence, mitochondrial dysfunction, and reduced mitochondrial membrane potential. The Annexin V/PI apoptosis detection assay, TUNEL assay, immunofluorescence, western blot, and real-time quantitative polymerase chain reaction assay showed that pretreatment with 1,25(OH)(2)D(3) could alleviate H(2)O(2)-induced NPMSC apoptosis, including the apoptosis rate and the expression of proapoptotic-related (Caspase-3 and Bax) and antiapoptotic-related (Bcl-2) proteins. The intracellular expression of p-Akt increased after pretreatment with 1,25(OH)(2)D(3). However, these protective effects of 1,25(OH)(2)D(3) were significantly decreased after the PI3K/Akt pathway was inhibited by the LY294002 treatment. In vivo, X-ray, MRI, and histological analyses showed that 1,25(OH)(2)D(3) treatment relieved the degree of IVDD in Sprague–Dawley rat disc puncture models. In summary, 1,25(OH)(2)D(3) efficiently attenuated oxidative stress-induced NPMSC apoptosis and mitochondrial dysfunction via PI3K/Akt pathway and is a promising candidate treatment for the repair of IVDD.
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spelling pubmed-89563842022-03-26 1,25(OH)(2)D(3) Mitigates Oxidative Stress-Induced Damage to Nucleus Pulposus-Derived Mesenchymal Stem Cells through PI3K/Akt Pathway Wang, Jun-wu Zhu, Lei Shi, Peng-zhi Wang, Ping-chuan Dai, Yan Wang, Yong-xiang Lu, Xu-hua Cheng, Xiao-fei Feng, Xin-min Zhang, Liang Oxid Med Cell Longev Research Article Intervertebral disc degeneration (IVDD) is one of the main causes of low back pain. The local environment of the degenerated intervertebral disc (IVD) increases oxidative stress and apoptosis of endogenous nucleus pulposus-derived mesenchymal stem cells (NPMSCs) and weakens its ability of endogenous repair ability in degenerated IVDs. A suitable concentration of 1α,25-dihydroxyvitamin D(3) (1,25(OH)(2)D(3)) has been certified to reduce oxidative stress and cell apoptosis. The current study investigated the protective effect and potential mechanism of 1,25(OH)(2)D(3) against oxidative stress-induced damage to NPMSCs. The present results showed that 1,25(OH)(2)D(3) showed a significant protective effect on NPMSCs at a concentration of 10(−10) M for 24 h. Protective effects of 1,25(OH)(2)D(3) were also exhibited against H(2)O(2)-induced NPMSC senescence, mitochondrial dysfunction, and reduced mitochondrial membrane potential. The Annexin V/PI apoptosis detection assay, TUNEL assay, immunofluorescence, western blot, and real-time quantitative polymerase chain reaction assay showed that pretreatment with 1,25(OH)(2)D(3) could alleviate H(2)O(2)-induced NPMSC apoptosis, including the apoptosis rate and the expression of proapoptotic-related (Caspase-3 and Bax) and antiapoptotic-related (Bcl-2) proteins. The intracellular expression of p-Akt increased after pretreatment with 1,25(OH)(2)D(3). However, these protective effects of 1,25(OH)(2)D(3) were significantly decreased after the PI3K/Akt pathway was inhibited by the LY294002 treatment. In vivo, X-ray, MRI, and histological analyses showed that 1,25(OH)(2)D(3) treatment relieved the degree of IVDD in Sprague–Dawley rat disc puncture models. In summary, 1,25(OH)(2)D(3) efficiently attenuated oxidative stress-induced NPMSC apoptosis and mitochondrial dysfunction via PI3K/Akt pathway and is a promising candidate treatment for the repair of IVDD. Hindawi 2022-03-18 /pmc/articles/PMC8956384/ /pubmed/35340208 http://dx.doi.org/10.1155/2022/1427110 Text en Copyright © 2022 Jun-wu Wang et al. https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Wang, Jun-wu
Zhu, Lei
Shi, Peng-zhi
Wang, Ping-chuan
Dai, Yan
Wang, Yong-xiang
Lu, Xu-hua
Cheng, Xiao-fei
Feng, Xin-min
Zhang, Liang
1,25(OH)(2)D(3) Mitigates Oxidative Stress-Induced Damage to Nucleus Pulposus-Derived Mesenchymal Stem Cells through PI3K/Akt Pathway
title 1,25(OH)(2)D(3) Mitigates Oxidative Stress-Induced Damage to Nucleus Pulposus-Derived Mesenchymal Stem Cells through PI3K/Akt Pathway
title_full 1,25(OH)(2)D(3) Mitigates Oxidative Stress-Induced Damage to Nucleus Pulposus-Derived Mesenchymal Stem Cells through PI3K/Akt Pathway
title_fullStr 1,25(OH)(2)D(3) Mitigates Oxidative Stress-Induced Damage to Nucleus Pulposus-Derived Mesenchymal Stem Cells through PI3K/Akt Pathway
title_full_unstemmed 1,25(OH)(2)D(3) Mitigates Oxidative Stress-Induced Damage to Nucleus Pulposus-Derived Mesenchymal Stem Cells through PI3K/Akt Pathway
title_short 1,25(OH)(2)D(3) Mitigates Oxidative Stress-Induced Damage to Nucleus Pulposus-Derived Mesenchymal Stem Cells through PI3K/Akt Pathway
title_sort 1,25(oh)(2)d(3) mitigates oxidative stress-induced damage to nucleus pulposus-derived mesenchymal stem cells through pi3k/akt pathway
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8956384/
https://www.ncbi.nlm.nih.gov/pubmed/35340208
http://dx.doi.org/10.1155/2022/1427110
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