Autophagy activation alleviates annulus fibrosus degeneration via the miR-2355-5p/mTOR pathway
Abstract Background Intervertebral disc degeneration disease (IVDD) is a major cause of disability and reduced work productivity worldwide. Annulus fibrosus degeneration is a key contributor to IVDD, yet its mechanisms remain poorly understood. Autophagy, a vital process for cellular homeostasis, in...
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| Format: | Article |
| Language: | English |
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BMC
2025-01-01
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| Series: | Journal of Orthopaedic Surgery and Research |
| Online Access: | https://doi.org/10.1186/s13018-025-05492-x |
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| author | Zilin Yu Chunyang Fan Yubo Mao Xiexing Wu Haiqing Mao |
| author_facet | Zilin Yu Chunyang Fan Yubo Mao Xiexing Wu Haiqing Mao |
| author_sort | Zilin Yu |
| collection | DOAJ |
| description | Abstract Background Intervertebral disc degeneration disease (IVDD) is a major cause of disability and reduced work productivity worldwide. Annulus fibrosus degeneration is a key contributor to IVDD, yet its mechanisms remain poorly understood. Autophagy, a vital process for cellular homeostasis, involves the lysosomal degradation of cytoplasmic proteins and organelles. This study aimed to investigate the role of autophagy in IVDD using a hydrogen peroxide (H2O2)-induced model of rat annulus fibrosus cells (AFCs). Methods AFCs were exposed to H2O2 to model oxidative stress-induced degeneration. Protein expression levels of collagen I, collagen II, MMP3, and MMP13 were quantified. GEO database analysis identified alterations in miR-2355-5p expression, and its regulatory role on the mTOR pathway and autophagy was assessed. Statistical tests were used to evaluate changes in protein expression and pathway activation. Results H2O2 exposure reduced collagen I and collagen II expression to approximately 50% of baseline levels, while MMP3 and MMP13 expression increased twofold. Activation of autophagy restored collagen I and II expression and decreased MMP3 and MMP13 levels. GEO analysis revealed significant alterations in miR-2355-5p expression, confirming its role in regulating the mTOR pathway and autophagy. Conclusions Autophagy, mediated by the miR-2355-5p/mTOR pathway, plays a protective role in AFCs degeneration. These findings suggest a potential therapeutic target for mitigating IVDD progression. |
| format | Article |
| id | doaj-art-c11043766d5b491d925172db392301c1 |
| institution | Kabale University |
| issn | 1749-799X |
| language | English |
| publishDate | 2025-01-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Orthopaedic Surgery and Research |
| spelling | doaj-art-c11043766d5b491d925172db392301c12025-01-26T12:43:18ZengBMCJournal of Orthopaedic Surgery and Research1749-799X2025-01-0120111310.1186/s13018-025-05492-xAutophagy activation alleviates annulus fibrosus degeneration via the miR-2355-5p/mTOR pathwayZilin Yu0Chunyang Fan1Yubo Mao2Xiexing Wu3Haiqing Mao4Orthopedic Institute, Department of Orthopaedic Surgery, The First Affiliated Hospital, Suzhou Medical College, Soochow UniversityOrthopedic Institute, Department of Orthopaedic Surgery, The First Affiliated Hospital, Suzhou Medical College, Soochow UniversityDepartment of Orthopedics, Wuxi Ninth People’s Hospital Affiliated to Soochow UniversityOrthopedic Institute, Department of Orthopaedic Surgery, The First Affiliated Hospital, Suzhou Medical College, Soochow UniversityOrthopedic Institute, Department of Orthopaedic Surgery, The First Affiliated Hospital, Suzhou Medical College, Soochow UniversityAbstract Background Intervertebral disc degeneration disease (IVDD) is a major cause of disability and reduced work productivity worldwide. Annulus fibrosus degeneration is a key contributor to IVDD, yet its mechanisms remain poorly understood. Autophagy, a vital process for cellular homeostasis, involves the lysosomal degradation of cytoplasmic proteins and organelles. This study aimed to investigate the role of autophagy in IVDD using a hydrogen peroxide (H2O2)-induced model of rat annulus fibrosus cells (AFCs). Methods AFCs were exposed to H2O2 to model oxidative stress-induced degeneration. Protein expression levels of collagen I, collagen II, MMP3, and MMP13 were quantified. GEO database analysis identified alterations in miR-2355-5p expression, and its regulatory role on the mTOR pathway and autophagy was assessed. Statistical tests were used to evaluate changes in protein expression and pathway activation. Results H2O2 exposure reduced collagen I and collagen II expression to approximately 50% of baseline levels, while MMP3 and MMP13 expression increased twofold. Activation of autophagy restored collagen I and II expression and decreased MMP3 and MMP13 levels. GEO analysis revealed significant alterations in miR-2355-5p expression, confirming its role in regulating the mTOR pathway and autophagy. Conclusions Autophagy, mediated by the miR-2355-5p/mTOR pathway, plays a protective role in AFCs degeneration. These findings suggest a potential therapeutic target for mitigating IVDD progression.https://doi.org/10.1186/s13018-025-05492-x |
| spellingShingle | Zilin Yu Chunyang Fan Yubo Mao Xiexing Wu Haiqing Mao Autophagy activation alleviates annulus fibrosus degeneration via the miR-2355-5p/mTOR pathway Journal of Orthopaedic Surgery and Research |
| title | Autophagy activation alleviates annulus fibrosus degeneration via the miR-2355-5p/mTOR pathway |
| title_full | Autophagy activation alleviates annulus fibrosus degeneration via the miR-2355-5p/mTOR pathway |
| title_fullStr | Autophagy activation alleviates annulus fibrosus degeneration via the miR-2355-5p/mTOR pathway |
| title_full_unstemmed | Autophagy activation alleviates annulus fibrosus degeneration via the miR-2355-5p/mTOR pathway |
| title_short | Autophagy activation alleviates annulus fibrosus degeneration via the miR-2355-5p/mTOR pathway |
| title_sort | autophagy activation alleviates annulus fibrosus degeneration via the mir 2355 5p mtor pathway |
| url | https://doi.org/10.1186/s13018-025-05492-x |
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