Bone mesenchymal stem cells based on matric hydrogels attenuate intervertebral disc degeneration by suppressing oxidative stress-induced ferroptosis
Abstract Intervertebral disc degeneration (IVDD) and its attendant lower back pain are a major medical challenge. Ferroptosis has become a new target for the treatment of IVDD. Mesenchymal stem cells (MSCs) are a promising regenerative therapy for IVDD. Hydrogel is usually used as a delivery carrier...
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Nature Portfolio
2025-05-01
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| Online Access: | https://doi.org/10.1038/s41598-025-00278-x |
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| author | Song Fu Renhua Lv Longqiang Wang Zhenyu Wang Fengming Wang Hao Gao Wei Zhao Xiaoling Huang Xiaojun Li Yanan Wang |
| author_facet | Song Fu Renhua Lv Longqiang Wang Zhenyu Wang Fengming Wang Hao Gao Wei Zhao Xiaoling Huang Xiaojun Li Yanan Wang |
| author_sort | Song Fu |
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| description | Abstract Intervertebral disc degeneration (IVDD) and its attendant lower back pain are a major medical challenge. Ferroptosis has become a new target for the treatment of IVDD. Mesenchymal stem cells (MSCs) are a promising regenerative therapy for IVDD. Hydrogel is usually used as a delivery carrier for MSCs. This study investigated the effect of bone mesenchymal stem cells (BMSCs) in IVDD by magnetic resonance imaging (MRI) and hematoxylin and eosin (HE) staining analysis using a rat-punctured IVDD model. A vitro model of tert-butyl hydroperoxide (TBHP)-induced oxidative stress injury in annulus fibrosus cells (AFCs) was used to explore the underlying molecular mechanisms. Cell viability was detected by cell counting kit-8 assay. Ferroptosis was assessed by measuring the levels of LDH, Fe2+, glutathione, lipid reactive oxygen species, and malondialdehyde. The underlying mechanism was investigated by western blot and phosphor-kinase array. Results suggested that BMSCs inhibited TBHP-induced ferroptosis and the phosphorylated levels of STAT3 in AFCs. The activation of STAT3 (colivelin, a specific agonist for STAT3) reversed the effects on the ferroptosis of BMSCs. Additionally, BMSCs alleviated IVDD progression based on matrix hydrogels, while colivelin abolished the protective effects of BMSCs-encapsulated hydrogels on IVDD. In short, BMSCs inhibited oxidative stress-induced AFCs ferroptosis, thereby alleviating IVDD, which is associated with inhibited STAT3 activation. This study demonstrated the possible underlying mechanism by which BMSCs mitigate IVDD and may provide a new therapeutic idea for IVDD. |
| format | Article |
| id | doaj-art-1dc8dff12426483bba008a732b551fae |
| institution | Kabale University |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj-art-1dc8dff12426483bba008a732b551fae2025-08-20T03:52:20ZengNature PortfolioScientific Reports2045-23222025-05-0115111110.1038/s41598-025-00278-xBone mesenchymal stem cells based on matric hydrogels attenuate intervertebral disc degeneration by suppressing oxidative stress-induced ferroptosisSong Fu0Renhua Lv1Longqiang Wang2Zhenyu Wang3Fengming Wang4Hao Gao5Wei Zhao6Xiaoling Huang7Xiaojun Li8Yanan Wang9Department of Minimally Invasive Spine Surgery, Shandong Wendeng Orthopedic HospitalDepartment of Neurology, Weihai Central HospitalDepartment of Minimally Invasive Spine Surgery, Shandong Wendeng Orthopedic HospitalDepartment of Minimally Invasive Spine Surgery, Shandong Wendeng Orthopedic HospitalDepartment of Minimally Invasive Spine Surgery, Shandong Wendeng Orthopedic HospitalDepartment of Minimally Invasive Spine Surgery, Shandong Wendeng Orthopedic HospitalDepartment of Minimally Invasive Spine Surgery, Shandong Wendeng Orthopedic HospitalDepartment of Minimally Invasive Spine Surgery, Shandong Wendeng Orthopedic HospitalDepartment of Minimally Invasive Spine Surgery, Shandong Wendeng Orthopedic HospitalDepartment of Minimally Invasive Spine Surgery, Shandong Wendeng Orthopedic HospitalAbstract Intervertebral disc degeneration (IVDD) and its attendant lower back pain are a major medical challenge. Ferroptosis has become a new target for the treatment of IVDD. Mesenchymal stem cells (MSCs) are a promising regenerative therapy for IVDD. Hydrogel is usually used as a delivery carrier for MSCs. This study investigated the effect of bone mesenchymal stem cells (BMSCs) in IVDD by magnetic resonance imaging (MRI) and hematoxylin and eosin (HE) staining analysis using a rat-punctured IVDD model. A vitro model of tert-butyl hydroperoxide (TBHP)-induced oxidative stress injury in annulus fibrosus cells (AFCs) was used to explore the underlying molecular mechanisms. Cell viability was detected by cell counting kit-8 assay. Ferroptosis was assessed by measuring the levels of LDH, Fe2+, glutathione, lipid reactive oxygen species, and malondialdehyde. The underlying mechanism was investigated by western blot and phosphor-kinase array. Results suggested that BMSCs inhibited TBHP-induced ferroptosis and the phosphorylated levels of STAT3 in AFCs. The activation of STAT3 (colivelin, a specific agonist for STAT3) reversed the effects on the ferroptosis of BMSCs. Additionally, BMSCs alleviated IVDD progression based on matrix hydrogels, while colivelin abolished the protective effects of BMSCs-encapsulated hydrogels on IVDD. In short, BMSCs inhibited oxidative stress-induced AFCs ferroptosis, thereby alleviating IVDD, which is associated with inhibited STAT3 activation. This study demonstrated the possible underlying mechanism by which BMSCs mitigate IVDD and may provide a new therapeutic idea for IVDD.https://doi.org/10.1038/s41598-025-00278-xIntervertebral disc degenerationBone mesenchymal stem cellMatric hydrogelsFerroptosisSTAT3 |
| spellingShingle | Song Fu Renhua Lv Longqiang Wang Zhenyu Wang Fengming Wang Hao Gao Wei Zhao Xiaoling Huang Xiaojun Li Yanan Wang Bone mesenchymal stem cells based on matric hydrogels attenuate intervertebral disc degeneration by suppressing oxidative stress-induced ferroptosis Scientific Reports Intervertebral disc degeneration Bone mesenchymal stem cell Matric hydrogels Ferroptosis STAT3 |
| title | Bone mesenchymal stem cells based on matric hydrogels attenuate intervertebral disc degeneration by suppressing oxidative stress-induced ferroptosis |
| title_full | Bone mesenchymal stem cells based on matric hydrogels attenuate intervertebral disc degeneration by suppressing oxidative stress-induced ferroptosis |
| title_fullStr | Bone mesenchymal stem cells based on matric hydrogels attenuate intervertebral disc degeneration by suppressing oxidative stress-induced ferroptosis |
| title_full_unstemmed | Bone mesenchymal stem cells based on matric hydrogels attenuate intervertebral disc degeneration by suppressing oxidative stress-induced ferroptosis |
| title_short | Bone mesenchymal stem cells based on matric hydrogels attenuate intervertebral disc degeneration by suppressing oxidative stress-induced ferroptosis |
| title_sort | bone mesenchymal stem cells based on matric hydrogels attenuate intervertebral disc degeneration by suppressing oxidative stress induced ferroptosis |
| topic | Intervertebral disc degeneration Bone mesenchymal stem cell Matric hydrogels Ferroptosis STAT3 |
| url | https://doi.org/10.1038/s41598-025-00278-x |
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