Stigmasterol alleviates endplate chondrocyte degeneration through inducing mitophagy by enhancing PINK1 mRNA acetylation via the ESR1/NAT10 axis
Intervertebral disc degeneration (IVDD) is a core factor in spinal degeneration. To date, there is no effective treatment for IVDD. It is urgent to identify the pathogenesis of IVDD to develop effective strategies for IVDD treatment. Alleviating endplate chondrocyte degeneration is a promising strat...
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De Gruyter
2025-04-01
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| Series: | Open Life Sciences |
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| Online Access: | https://doi.org/10.1515/biol-2022-0913 |
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| author | Li Hao Chen Xiaofeng Huang Baoci He Junjie Xie Junxian Guo Weijun Liang Jinjun Ruan Jiajian Liu Jincheng Xiang Zhen Zhu Lixin |
| author_facet | Li Hao Chen Xiaofeng Huang Baoci He Junjie Xie Junxian Guo Weijun Liang Jinjun Ruan Jiajian Liu Jincheng Xiang Zhen Zhu Lixin |
| author_sort | Li Hao |
| collection | DOAJ |
| description | Intervertebral disc degeneration (IVDD) is a core factor in spinal degeneration. To date, there is no effective treatment for IVDD. It is urgent to identify the pathogenesis of IVDD to develop effective strategies for IVDD treatment. Alleviating endplate chondrocyte degeneration is a promising strategy for IVDD treatment, while mitophagy prevents degeneration of endplate chondrocytes. Stigmasterol (STM) protects neurons from injuries by triggering mitophagy, yet the effect of STM on the mitophagy of endplate chondrocytes in IVDD has not been reported. In this study, endplate chondrocyte degeneration was induced by interleukin-1β, and the ribonucleic acid (RNA) acetylation level was identified by acetylated RNA immunoprecipitation. Herein, results indicated that STM alleviated endplate chondrocyte degeneration. Besides, STM induced PTEN-induced kinase 1 (PINK1)-mediated mitophagy in degenerated endplate chondrocytes. Moreover, N‐acetyltransferase 10 (NAT10) increased PINK1 expression by improving PINK1 mRNA acetylation in endplate chondrocytes. In addition, STM regulated NAT10 expression by estrogen receptor 1 (ESR1) in degenerated endplate chondrocytes. In summary, the present study revealed that STM attenuated endplate chondrocyte degeneration through inducing mitophagy by enhancing PINK1 mRNA acetylation via the ESR1/NAT10 axis. These findings would provide novel strategies for the treatment of IVDD. |
| format | Article |
| id | doaj-art-18f042770a6842e885a4681006fa3168 |
| institution | OA Journals |
| issn | 2391-5412 |
| language | English |
| publishDate | 2025-04-01 |
| publisher | De Gruyter |
| record_format | Article |
| series | Open Life Sciences |
| spelling | doaj-art-18f042770a6842e885a4681006fa31682025-08-20T02:17:10ZengDe GruyterOpen Life Sciences2391-54122025-04-0120115796010.1515/biol-2022-0913Stigmasterol alleviates endplate chondrocyte degeneration through inducing mitophagy by enhancing PINK1 mRNA acetylation via the ESR1/NAT10 axisLi Hao0Chen Xiaofeng1Huang Baoci2He Junjie3Xie Junxian4Guo Weijun5Liang Jinjun6Ruan Jiajian7Liu Jincheng8Xiang Zhen9Zhu Lixin10Department of Spinal Surgery, Orthopedic Medical Center, Zhujiang Hospital, Southern Medical University, Guangzhou510280, ChinaDepartment of Orthopedics, Panyu Hospital of Chinese Medicine, Guangzhou, Guangdong511400, ChinaDepartment of Ultrasound, Guangdong Second Provincial General Hospital, Guangzhou, Guangdong510310, ChinaDepartment of Spinal Surgery, Orthopedic Medical Center, Zhujiang Hospital, Southern Medical University, Guangzhou510280, ChinaDepartment of Orthopedics, Panyu Hospital of Chinese Medicine, Guangzhou, Guangdong511400, ChinaDepartment of Orthopedics, Panyu Hospital of Chinese Medicine, Guangzhou, Guangdong511400, ChinaDepartment of Orthopedics, Panyu Hospital of Chinese Medicine, Guangzhou, Guangdong511400, ChinaDepartment of Orthopedics, Panyu Hospital of Chinese Medicine, Guangzhou, Guangdong511400, ChinaDepartment of Orthopedics, Panyu Hospital of Chinese Medicine, Guangzhou, Guangdong511400, ChinaDepartment of Orthopedics, Panyu Hospital of Chinese Medicine, Guangzhou, Guangdong511400, ChinaDepartment of Spinal Surgery, Orthopedic Medical Center, Zhujiang Hospital, Southern Medical University, Guangzhou510280, ChinaIntervertebral disc degeneration (IVDD) is a core factor in spinal degeneration. To date, there is no effective treatment for IVDD. It is urgent to identify the pathogenesis of IVDD to develop effective strategies for IVDD treatment. Alleviating endplate chondrocyte degeneration is a promising strategy for IVDD treatment, while mitophagy prevents degeneration of endplate chondrocytes. Stigmasterol (STM) protects neurons from injuries by triggering mitophagy, yet the effect of STM on the mitophagy of endplate chondrocytes in IVDD has not been reported. In this study, endplate chondrocyte degeneration was induced by interleukin-1β, and the ribonucleic acid (RNA) acetylation level was identified by acetylated RNA immunoprecipitation. Herein, results indicated that STM alleviated endplate chondrocyte degeneration. Besides, STM induced PTEN-induced kinase 1 (PINK1)-mediated mitophagy in degenerated endplate chondrocytes. Moreover, N‐acetyltransferase 10 (NAT10) increased PINK1 expression by improving PINK1 mRNA acetylation in endplate chondrocytes. In addition, STM regulated NAT10 expression by estrogen receptor 1 (ESR1) in degenerated endplate chondrocytes. In summary, the present study revealed that STM attenuated endplate chondrocyte degeneration through inducing mitophagy by enhancing PINK1 mRNA acetylation via the ESR1/NAT10 axis. These findings would provide novel strategies for the treatment of IVDD.https://doi.org/10.1515/biol-2022-0913intervertebral disc degenerationendplate chondrocyte degenerationstigmasterolmitophagyrna acetylation |
| spellingShingle | Li Hao Chen Xiaofeng Huang Baoci He Junjie Xie Junxian Guo Weijun Liang Jinjun Ruan Jiajian Liu Jincheng Xiang Zhen Zhu Lixin Stigmasterol alleviates endplate chondrocyte degeneration through inducing mitophagy by enhancing PINK1 mRNA acetylation via the ESR1/NAT10 axis Open Life Sciences intervertebral disc degeneration endplate chondrocyte degeneration stigmasterol mitophagy rna acetylation |
| title | Stigmasterol alleviates endplate chondrocyte degeneration through inducing mitophagy by enhancing PINK1 mRNA acetylation via the ESR1/NAT10 axis |
| title_full | Stigmasterol alleviates endplate chondrocyte degeneration through inducing mitophagy by enhancing PINK1 mRNA acetylation via the ESR1/NAT10 axis |
| title_fullStr | Stigmasterol alleviates endplate chondrocyte degeneration through inducing mitophagy by enhancing PINK1 mRNA acetylation via the ESR1/NAT10 axis |
| title_full_unstemmed | Stigmasterol alleviates endplate chondrocyte degeneration through inducing mitophagy by enhancing PINK1 mRNA acetylation via the ESR1/NAT10 axis |
| title_short | Stigmasterol alleviates endplate chondrocyte degeneration through inducing mitophagy by enhancing PINK1 mRNA acetylation via the ESR1/NAT10 axis |
| title_sort | stigmasterol alleviates endplate chondrocyte degeneration through inducing mitophagy by enhancing pink1 mrna acetylation via the esr1 nat10 axis |
| topic | intervertebral disc degeneration endplate chondrocyte degeneration stigmasterol mitophagy rna acetylation |
| url | https://doi.org/10.1515/biol-2022-0913 |
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