SND1 aggravates mitochondrial damage, apoptosis and extracellular matrix degradation in IL-1β-stimulated chondrocytes via PINK1/BECN1 pathway
Abstract Recently, evidence has suggested a regulatory role for SND1 in osteoarthritis progression. Interestingly, we found that SND1 protein expression was increased, mitochondria were shrunken and decreased in number, mitochondrial membrane potential was decreased, mitochondrial ROS production was...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2023-09-01
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| Series: | European Journal of Medical Research |
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| Online Access: | https://doi.org/10.1186/s40001-023-01340-y |
| _version_ | 1797453515506843648 |
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| author | Shufeng Lin Huiyang Guo Xiaoxuan You Zefeng Zhang Hui Ye |
| author_facet | Shufeng Lin Huiyang Guo Xiaoxuan You Zefeng Zhang Hui Ye |
| author_sort | Shufeng Lin |
| collection | DOAJ |
| description | Abstract Recently, evidence has suggested a regulatory role for SND1 in osteoarthritis progression. Interestingly, we found that SND1 protein expression was increased, mitochondria were shrunken and decreased in number, mitochondrial membrane potential was decreased, mitochondrial ROS production was increased, and ATP levels were decreased in IL-1β treated mouse chondrocytes, and SND1 silencing removed these changes. Furthermore, IL-1β treatment promoted inflammatory factor secretion in chondrocytes, promoted cell apoptosis, increased MMP13 protein and inhibited collagen II protein expression, and si-SND1 inhibited the IL-1β effects. We validated the association between SND1 and PINK1 and found that PINK1 reversed the inhibitory effects of SND1 silencing on IL-1β-induced mitochondrial damage, inflammatory reaction, apoptosis and extracellular matrix degradation in mouse chondrocytes. Furthermore, we found that PINK1 upregulated BECN1 protein expression and that BECN reversed the inhibitory effects of PINK1 silencing on IL-1β-induced mitochondrial damage, inflammatory reaction, apoptosis and extracellular matrix degradation. Further mechanistic studies revealed that PINK1 inhibited the AMPK/mTOR signaling axis to aggravate IL-1β induced mouse chondrocytes injury by upregulating BECN1 protein expression. In vivo results showed that the damage to cartilage tissue was significantly alleviated in rats with osteoarthritis by knocking down SND1 expression. |
| first_indexed | 2024-03-09T15:23:58Z |
| format | Article |
| id | doaj.art-fdda41c63e594b2d9f7ed07eba657f66 |
| institution | Directory Open Access Journal |
| issn | 2047-783X |
| language | English |
| last_indexed | 2024-03-09T15:23:58Z |
| publishDate | 2023-09-01 |
| publisher | BMC |
| record_format | Article |
| series | European Journal of Medical Research |
| spelling | doaj.art-fdda41c63e594b2d9f7ed07eba657f662023-11-26T12:41:55ZengBMCEuropean Journal of Medical Research2047-783X2023-09-0128111310.1186/s40001-023-01340-ySND1 aggravates mitochondrial damage, apoptosis and extracellular matrix degradation in IL-1β-stimulated chondrocytes via PINK1/BECN1 pathwayShufeng Lin0Huiyang Guo1Xiaoxuan You2Zefeng Zhang3Hui Ye4Department of Orthopedics, The Second Affiliated Hospital of Fujian Medical UniversityDepartment of Orthopedics, The Second Affiliated Hospital of Fujian Medical UniversityDepartment of Orthopedics, The Second Affiliated Hospital of Fujian Medical UniversityDepartment of Orthopedics, The Second Affiliated Hospital of Fujian Medical UniversityDepartment of Orthopedics, The Second Affiliated Hospital of Fujian Medical UniversityAbstract Recently, evidence has suggested a regulatory role for SND1 in osteoarthritis progression. Interestingly, we found that SND1 protein expression was increased, mitochondria were shrunken and decreased in number, mitochondrial membrane potential was decreased, mitochondrial ROS production was increased, and ATP levels were decreased in IL-1β treated mouse chondrocytes, and SND1 silencing removed these changes. Furthermore, IL-1β treatment promoted inflammatory factor secretion in chondrocytes, promoted cell apoptosis, increased MMP13 protein and inhibited collagen II protein expression, and si-SND1 inhibited the IL-1β effects. We validated the association between SND1 and PINK1 and found that PINK1 reversed the inhibitory effects of SND1 silencing on IL-1β-induced mitochondrial damage, inflammatory reaction, apoptosis and extracellular matrix degradation in mouse chondrocytes. Furthermore, we found that PINK1 upregulated BECN1 protein expression and that BECN reversed the inhibitory effects of PINK1 silencing on IL-1β-induced mitochondrial damage, inflammatory reaction, apoptosis and extracellular matrix degradation. Further mechanistic studies revealed that PINK1 inhibited the AMPK/mTOR signaling axis to aggravate IL-1β induced mouse chondrocytes injury by upregulating BECN1 protein expression. In vivo results showed that the damage to cartilage tissue was significantly alleviated in rats with osteoarthritis by knocking down SND1 expression.https://doi.org/10.1186/s40001-023-01340-yOsteoarthritisSND1MitochondrialExtracellular matrixThe PINK1BECN1 pathway |
| spellingShingle | Shufeng Lin Huiyang Guo Xiaoxuan You Zefeng Zhang Hui Ye SND1 aggravates mitochondrial damage, apoptosis and extracellular matrix degradation in IL-1β-stimulated chondrocytes via PINK1/BECN1 pathway European Journal of Medical Research Osteoarthritis SND1 Mitochondrial Extracellular matrix The PINK1 BECN1 pathway |
| title | SND1 aggravates mitochondrial damage, apoptosis and extracellular matrix degradation in IL-1β-stimulated chondrocytes via PINK1/BECN1 pathway |
| title_full | SND1 aggravates mitochondrial damage, apoptosis and extracellular matrix degradation in IL-1β-stimulated chondrocytes via PINK1/BECN1 pathway |
| title_fullStr | SND1 aggravates mitochondrial damage, apoptosis and extracellular matrix degradation in IL-1β-stimulated chondrocytes via PINK1/BECN1 pathway |
| title_full_unstemmed | SND1 aggravates mitochondrial damage, apoptosis and extracellular matrix degradation in IL-1β-stimulated chondrocytes via PINK1/BECN1 pathway |
| title_short | SND1 aggravates mitochondrial damage, apoptosis and extracellular matrix degradation in IL-1β-stimulated chondrocytes via PINK1/BECN1 pathway |
| title_sort | snd1 aggravates mitochondrial damage apoptosis and extracellular matrix degradation in il 1β stimulated chondrocytes via pink1 becn1 pathway |
| topic | Osteoarthritis SND1 Mitochondrial Extracellular matrix The PINK1 BECN1 pathway |
| url | https://doi.org/10.1186/s40001-023-01340-y |
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