Upregulating miR-181b promotes ferroptosis in osteoarthritic chondrocytes by inhibiting SLC7A11
Abstract Background Osteoarthritis (OA) is a common disease with a complex pathology. This study aimed to investigate the correlation between the aberrant upregulation of miR-181b and ferroptosis in chondrocytes during the progression of OA. Methods An OA cell model was constructed with erastin. Fer...
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BMC
2023-11-01
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| Series: | BMC Musculoskeletal Disorders |
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| Online Access: | https://doi.org/10.1186/s12891-023-07003-7 |
| _version_ | 1797630420256292864 |
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| author | Dexin Wang Yu Fang Liang Lin Wensuo Long Lei Wang Liwei Yu Huaiming Deng Dan Wang |
| author_facet | Dexin Wang Yu Fang Liang Lin Wensuo Long Lei Wang Liwei Yu Huaiming Deng Dan Wang |
| author_sort | Dexin Wang |
| collection | DOAJ |
| description | Abstract Background Osteoarthritis (OA) is a common disease with a complex pathology. This study aimed to investigate the correlation between the aberrant upregulation of miR-181b and ferroptosis in chondrocytes during the progression of OA. Methods An OA cell model was constructed with erastin. Ferrostatin-1 (Fer), bioinformatics, and dual-luciferase activity reports were used to investigate the effect of miR-181b on OA. Finally, a rat model of OA was induced by monosodium iodoacetate to verify that miR-181b inhibits SLC7A11 gene expression and increases ferroptosis. Results The results showed that Fer could effectively reverse the erastin-induced inhibition of human chondrocyte viability, increase the level of collagenous proteins in human chondrocytes, and inhibit oxidative stress and ferroptosis. MiR-181b is abnormally elevated in OA cell models. Transfection of a miR-181b inhibitor could increase the expression levels of the ferroptosis-related proteins solute carrier family 7 members 11 (SLC7A11) and glutathione peroxidase 4 (GPX4), thereby inhibiting the occurrence of ferroptosis in chondrocytes. In addition, hsa-miR-181b-5p and SLC7A11 have a targeted regulatory effect. Transfection of SLC7A11 siRNA effectively abrogated the increase in chondrocyte viability induced by the miR-181 inhibitor and increased ferroptosis. Finally, miR-181b was shown to exacerbate OA disease progression by inhibiting SLC7A11 gene expression and increasing ferroptosis in a rat OA model. Conclusions Elevating miR-181b may mediate chondrocyte ferroptosis by targeting SLC7A11 in OA. |
| first_indexed | 2024-03-11T11:08:04Z |
| format | Article |
| id | doaj.art-00c04c2a40014e629244cfd3a6863f3e |
| institution | Directory Open Access Journal |
| issn | 1471-2474 |
| language | English |
| last_indexed | 2024-03-11T11:08:04Z |
| publishDate | 2023-11-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Musculoskeletal Disorders |
| spelling | doaj.art-00c04c2a40014e629244cfd3a6863f3e2023-11-12T12:04:08ZengBMCBMC Musculoskeletal Disorders1471-24742023-11-0124111210.1186/s12891-023-07003-7Upregulating miR-181b promotes ferroptosis in osteoarthritic chondrocytes by inhibiting SLC7A11Dexin Wang0Yu Fang1Liang Lin2Wensuo Long3Lei Wang4Liwei Yu5Huaiming Deng6Dan Wang7Department of Orthopaedics, Haishu Branch, Ningbo First HospitalDepartment of Orthopaedics, Haishu Branch, Ningbo First HospitalDepartment of Orthopaedics, Haishu Branch, Ningbo First HospitalDepartment of Orthopaedics, Haishu Branch, Ningbo First HospitalDepartment of Orthopaedics, Haishu Branch, Ningbo First HospitalDepartment of Orthopaedics, Haishu Branch, Ningbo First HospitalDepartment of Orthopaedics, Haishu Branch, Ningbo First HospitalDepartment of Pharmacology, Medical College of Dalian UniversityAbstract Background Osteoarthritis (OA) is a common disease with a complex pathology. This study aimed to investigate the correlation between the aberrant upregulation of miR-181b and ferroptosis in chondrocytes during the progression of OA. Methods An OA cell model was constructed with erastin. Ferrostatin-1 (Fer), bioinformatics, and dual-luciferase activity reports were used to investigate the effect of miR-181b on OA. Finally, a rat model of OA was induced by monosodium iodoacetate to verify that miR-181b inhibits SLC7A11 gene expression and increases ferroptosis. Results The results showed that Fer could effectively reverse the erastin-induced inhibition of human chondrocyte viability, increase the level of collagenous proteins in human chondrocytes, and inhibit oxidative stress and ferroptosis. MiR-181b is abnormally elevated in OA cell models. Transfection of a miR-181b inhibitor could increase the expression levels of the ferroptosis-related proteins solute carrier family 7 members 11 (SLC7A11) and glutathione peroxidase 4 (GPX4), thereby inhibiting the occurrence of ferroptosis in chondrocytes. In addition, hsa-miR-181b-5p and SLC7A11 have a targeted regulatory effect. Transfection of SLC7A11 siRNA effectively abrogated the increase in chondrocyte viability induced by the miR-181 inhibitor and increased ferroptosis. Finally, miR-181b was shown to exacerbate OA disease progression by inhibiting SLC7A11 gene expression and increasing ferroptosis in a rat OA model. Conclusions Elevating miR-181b may mediate chondrocyte ferroptosis by targeting SLC7A11 in OA.https://doi.org/10.1186/s12891-023-07003-7OsteoarthritisChondrocytesFerroptosismiR-181b-5pSLC7A11 |
| spellingShingle | Dexin Wang Yu Fang Liang Lin Wensuo Long Lei Wang Liwei Yu Huaiming Deng Dan Wang Upregulating miR-181b promotes ferroptosis in osteoarthritic chondrocytes by inhibiting SLC7A11 BMC Musculoskeletal Disorders Osteoarthritis Chondrocytes Ferroptosis miR-181b-5p SLC7A11 |
| title | Upregulating miR-181b promotes ferroptosis in osteoarthritic chondrocytes by inhibiting SLC7A11 |
| title_full | Upregulating miR-181b promotes ferroptosis in osteoarthritic chondrocytes by inhibiting SLC7A11 |
| title_fullStr | Upregulating miR-181b promotes ferroptosis in osteoarthritic chondrocytes by inhibiting SLC7A11 |
| title_full_unstemmed | Upregulating miR-181b promotes ferroptosis in osteoarthritic chondrocytes by inhibiting SLC7A11 |
| title_short | Upregulating miR-181b promotes ferroptosis in osteoarthritic chondrocytes by inhibiting SLC7A11 |
| title_sort | upregulating mir 181b promotes ferroptosis in osteoarthritic chondrocytes by inhibiting slc7a11 |
| topic | Osteoarthritis Chondrocytes Ferroptosis miR-181b-5p SLC7A11 |
| url | https://doi.org/10.1186/s12891-023-07003-7 |
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