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Strontium Ranelate Ameliorates Intervertebral Disc Degeneration via Regulating TGF-β1/NF-κB Axis
Intervertebral disc degeneration (IVDD) is a prevalent and debilitating condition characterized by chronic back pain and reduced quality of life. Strontium ranelate (SRR) is a compound traditionally used for treating osteoporosis via activating TGF-β1 signaling pathway. Recent studies have proved th...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Ivyspring International Publisher
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10620869/ https://www.ncbi.nlm.nih.gov/pubmed/37928874 http://dx.doi.org/10.7150/ijms.86665 |
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author | Sun, Ruping Zhu, Jian Sun, Kaiqiang Gao, Lu Zheng, Bing Shi, Jiangang |
author_facet | Sun, Ruping Zhu, Jian Sun, Kaiqiang Gao, Lu Zheng, Bing Shi, Jiangang |
author_sort | Sun, Ruping |
collection | PubMed |
description | Intervertebral disc degeneration (IVDD) is a prevalent and debilitating condition characterized by chronic back pain and reduced quality of life. Strontium ranelate (SRR) is a compound traditionally used for treating osteoporosis via activating TGF-β1 signaling pathway. Recent studies have proved the anti-inflammatory effect of SRR on chondrocytes. Although the exact mechanism of IVDD remains unclear, accumulating evidences have emphasized the involvement of multifactorial pathogenesis including inflammation, oxidative stress damage, and etc. However, the biological effect of SRR on IVDD and its molecular mechanism has not been investigated. Firstly, this study proved the decreased expression of Transforming Growth Factor-beta 1(TGF-β1) in degenerated human intervertebral disc tissues. Subsequently, we confirmed for the first time that SRR could promote cell proliferation, mitigate inflammation and oxidative stress in human nucleus pulposus cells in vitro via increasing the expression of TGF-β1 and suppressing the Nuclear Factor Kappa-Light-Chain-Enhancer of Activated B Cells (NF-κB) pathway. The molecular docking result proved the interaction between SRR and TGF-β1 protein. To further verify this interaction, gain- and loss- of function experiments were conducted. We discovered that both TGF-β1 knockdown and overexpression influenced the activation of the NF-κB pathway. Taken together, SRR could mitigate IL-1β induced-cell dysfunction in human nucleus pulposus cells by regulating TGF-β1/NF-κB axis in vitro. Finally, the in vivo therapeutic effect of SRR on IVDD was confirmed. Our findings may contribute to the understanding of the complex interplay between inflammation and degenerative processes in the intervertebral disc and provide valuable insights into the development of targeted treatment-based therapeutics for IVDD. |
format | Online Article Text |
id | pubmed-10620869 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Ivyspring International Publisher |
record_format | MEDLINE/PubMed |
spelling | pubmed-106208692023-11-03 Strontium Ranelate Ameliorates Intervertebral Disc Degeneration via Regulating TGF-β1/NF-κB Axis Sun, Ruping Zhu, Jian Sun, Kaiqiang Gao, Lu Zheng, Bing Shi, Jiangang Int J Med Sci Research Paper Intervertebral disc degeneration (IVDD) is a prevalent and debilitating condition characterized by chronic back pain and reduced quality of life. Strontium ranelate (SRR) is a compound traditionally used for treating osteoporosis via activating TGF-β1 signaling pathway. Recent studies have proved the anti-inflammatory effect of SRR on chondrocytes. Although the exact mechanism of IVDD remains unclear, accumulating evidences have emphasized the involvement of multifactorial pathogenesis including inflammation, oxidative stress damage, and etc. However, the biological effect of SRR on IVDD and its molecular mechanism has not been investigated. Firstly, this study proved the decreased expression of Transforming Growth Factor-beta 1(TGF-β1) in degenerated human intervertebral disc tissues. Subsequently, we confirmed for the first time that SRR could promote cell proliferation, mitigate inflammation and oxidative stress in human nucleus pulposus cells in vitro via increasing the expression of TGF-β1 and suppressing the Nuclear Factor Kappa-Light-Chain-Enhancer of Activated B Cells (NF-κB) pathway. The molecular docking result proved the interaction between SRR and TGF-β1 protein. To further verify this interaction, gain- and loss- of function experiments were conducted. We discovered that both TGF-β1 knockdown and overexpression influenced the activation of the NF-κB pathway. Taken together, SRR could mitigate IL-1β induced-cell dysfunction in human nucleus pulposus cells by regulating TGF-β1/NF-κB axis in vitro. Finally, the in vivo therapeutic effect of SRR on IVDD was confirmed. Our findings may contribute to the understanding of the complex interplay between inflammation and degenerative processes in the intervertebral disc and provide valuable insights into the development of targeted treatment-based therapeutics for IVDD. Ivyspring International Publisher 2023-10-07 /pmc/articles/PMC10620869/ /pubmed/37928874 http://dx.doi.org/10.7150/ijms.86665 Text en © The author(s) https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/). See http://ivyspring.com/terms for full terms and conditions. |
spellingShingle | Research Paper Sun, Ruping Zhu, Jian Sun, Kaiqiang Gao, Lu Zheng, Bing Shi, Jiangang Strontium Ranelate Ameliorates Intervertebral Disc Degeneration via Regulating TGF-β1/NF-κB Axis |
title | Strontium Ranelate Ameliorates Intervertebral Disc Degeneration via Regulating TGF-β1/NF-κB Axis |
title_full | Strontium Ranelate Ameliorates Intervertebral Disc Degeneration via Regulating TGF-β1/NF-κB Axis |
title_fullStr | Strontium Ranelate Ameliorates Intervertebral Disc Degeneration via Regulating TGF-β1/NF-κB Axis |
title_full_unstemmed | Strontium Ranelate Ameliorates Intervertebral Disc Degeneration via Regulating TGF-β1/NF-κB Axis |
title_short | Strontium Ranelate Ameliorates Intervertebral Disc Degeneration via Regulating TGF-β1/NF-κB Axis |
title_sort | strontium ranelate ameliorates intervertebral disc degeneration via regulating tgf-β1/nf-κb axis |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10620869/ https://www.ncbi.nlm.nih.gov/pubmed/37928874 http://dx.doi.org/10.7150/ijms.86665 |
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