Moderate mechanical stress suppresses chondrocyte ferroptosis in osteoarthritis by regulating NF-κB p65/GPX4 signaling pathway
Abstract Ferroptosis is a recently identified form of programmed cell death that plays an important role in the pathophysiological process of osteoarthritis (OA). Herein, we investigated the protective effect of moderate mechanical stress on chondrocyte ferroptosis and further revealed the internal...
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Nature Portfolio
2024-03-01
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| Series: | Scientific Reports |
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| Online Access: | https://doi.org/10.1038/s41598-024-55629-x |
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| author | Juanjuan Han Li-nan Zhan Yue Huang Shijia Guo Xiaoding Zhou Leonid Kapilevich Zhuo Wang Ke Ning Mingli Sun Xin-an Zhang |
| author_facet | Juanjuan Han Li-nan Zhan Yue Huang Shijia Guo Xiaoding Zhou Leonid Kapilevich Zhuo Wang Ke Ning Mingli Sun Xin-an Zhang |
| author_sort | Juanjuan Han |
| collection | DOAJ |
| description | Abstract Ferroptosis is a recently identified form of programmed cell death that plays an important role in the pathophysiological process of osteoarthritis (OA). Herein, we investigated the protective effect of moderate mechanical stress on chondrocyte ferroptosis and further revealed the internal molecular mechanism. Intra-articular injection of sodium iodoacetate (MIA) was conducted to induce the rat model of OA in vivo, meanwhile, interleukin-1 beta (IL-1β) was treated to chondrocytes to induce the OA cell model in vitro. The OA phenotype was analyzed by histology and microcomputed tomography, the ferroptosis was analyzed by transmission electron microscope and immunofluorescence. The expression of ferroptosis and cartilage metabolism-related factors was analyzed by immunohistochemical and Western blot. Animal experiments revealed that moderate-intensity treadmill exercise could effectively reduce chondrocyte ferroptosis and cartilage matrix degradation in MIA-induced OA rats. Cell experiments showed that 4-h cyclic tensile strain intervention could activate Nrf2 and inhibit the NF-κB signaling pathway, increase the expression of Col2a1, GPX4, and SLC7A11, decrease the expression of MMP13 and P53, thereby restraining IL-1β-induced chondrocyte ferroptosis and degeneration. Inhibition of NF-κB signaling pathway relieved the chondrocyte ferroptosis and degeneration. Meanwhile, overexpression of NF-κB by recombinant lentivirus reversed the positive effect of CTS on chondrocytes. Moderate mechanical stress could activate the Nrf2 antioxidant system, inhibit the NF-κB p65 signaling pathway, and inhibit chondrocyte ferroptosis and cartilage matrix degradation by regulating P53, SLC7A11, and GPX4. |
| first_indexed | 2024-03-07T15:06:41Z |
| format | Article |
| id | doaj.art-e59cd436a338433eaa9275e66f772a0a |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-03-07T15:06:41Z |
| publishDate | 2024-03-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-e59cd436a338433eaa9275e66f772a0a2024-03-05T18:54:25ZengNature PortfolioScientific Reports2045-23222024-03-0114111510.1038/s41598-024-55629-xModerate mechanical stress suppresses chondrocyte ferroptosis in osteoarthritis by regulating NF-κB p65/GPX4 signaling pathwayJuanjuan Han0Li-nan Zhan1Yue Huang2Shijia Guo3Xiaoding Zhou4Leonid Kapilevich5Zhuo Wang6Ke Ning7Mingli Sun8Xin-an Zhang9College of Exercise and Health, Shenyang Sport UniversityCollege of Exercise and Health, Shenyang Sport UniversityCollege of Exercise and Health, Shenyang Sport UniversityCollege of Exercise and Health, Shenyang Sport UniversityCollege of Exercise and Health, Shenyang Sport UniversityFaculty of Physical Education, National Research Tomsk State UniversityCollege of Exercise and Health, Shenyang Sport UniversityCollege of Exercise and Health, Shenyang Sport UniversityCollege of Exercise and Health, Shenyang Sport UniversityCollege of Exercise and Health, Shenyang Sport UniversityAbstract Ferroptosis is a recently identified form of programmed cell death that plays an important role in the pathophysiological process of osteoarthritis (OA). Herein, we investigated the protective effect of moderate mechanical stress on chondrocyte ferroptosis and further revealed the internal molecular mechanism. Intra-articular injection of sodium iodoacetate (MIA) was conducted to induce the rat model of OA in vivo, meanwhile, interleukin-1 beta (IL-1β) was treated to chondrocytes to induce the OA cell model in vitro. The OA phenotype was analyzed by histology and microcomputed tomography, the ferroptosis was analyzed by transmission electron microscope and immunofluorescence. The expression of ferroptosis and cartilage metabolism-related factors was analyzed by immunohistochemical and Western blot. Animal experiments revealed that moderate-intensity treadmill exercise could effectively reduce chondrocyte ferroptosis and cartilage matrix degradation in MIA-induced OA rats. Cell experiments showed that 4-h cyclic tensile strain intervention could activate Nrf2 and inhibit the NF-κB signaling pathway, increase the expression of Col2a1, GPX4, and SLC7A11, decrease the expression of MMP13 and P53, thereby restraining IL-1β-induced chondrocyte ferroptosis and degeneration. Inhibition of NF-κB signaling pathway relieved the chondrocyte ferroptosis and degeneration. Meanwhile, overexpression of NF-κB by recombinant lentivirus reversed the positive effect of CTS on chondrocytes. Moderate mechanical stress could activate the Nrf2 antioxidant system, inhibit the NF-κB p65 signaling pathway, and inhibit chondrocyte ferroptosis and cartilage matrix degradation by regulating P53, SLC7A11, and GPX4.https://doi.org/10.1038/s41598-024-55629-xMechanical stressOsteoarthritisFerroptosisCartilage |
| spellingShingle | Juanjuan Han Li-nan Zhan Yue Huang Shijia Guo Xiaoding Zhou Leonid Kapilevich Zhuo Wang Ke Ning Mingli Sun Xin-an Zhang Moderate mechanical stress suppresses chondrocyte ferroptosis in osteoarthritis by regulating NF-κB p65/GPX4 signaling pathway Scientific Reports Mechanical stress Osteoarthritis Ferroptosis Cartilage |
| title | Moderate mechanical stress suppresses chondrocyte ferroptosis in osteoarthritis by regulating NF-κB p65/GPX4 signaling pathway |
| title_full | Moderate mechanical stress suppresses chondrocyte ferroptosis in osteoarthritis by regulating NF-κB p65/GPX4 signaling pathway |
| title_fullStr | Moderate mechanical stress suppresses chondrocyte ferroptosis in osteoarthritis by regulating NF-κB p65/GPX4 signaling pathway |
| title_full_unstemmed | Moderate mechanical stress suppresses chondrocyte ferroptosis in osteoarthritis by regulating NF-κB p65/GPX4 signaling pathway |
| title_short | Moderate mechanical stress suppresses chondrocyte ferroptosis in osteoarthritis by regulating NF-κB p65/GPX4 signaling pathway |
| title_sort | moderate mechanical stress suppresses chondrocyte ferroptosis in osteoarthritis by regulating nf κb p65 gpx4 signaling pathway |
| topic | Mechanical stress Osteoarthritis Ferroptosis Cartilage |
| url | https://doi.org/10.1038/s41598-024-55629-x |
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