Omaveloxolone inhibits IL-1β-induced chondrocyte apoptosis through the Nrf2/ARE and NF-κB signalling pathways in vitro and attenuates osteoarthritis in vivo
Osteoarthritis (OA) is a common degenerative joint disease. Effective drugs that can halt or decelerate osteoarthritis progression are still lacking. Omaveloxolone is a semisynthetic oleanane triterpenoid exerting antioxidative and anti-inflammatory effects. The present study aims to determine wheth...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-09-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2022.952950/full |
| _version_ | 1811258371309830144 |
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| author | Zengxin Jiang Zengxin Jiang Guobin Qi Wei Lu Hao Wang Defang Li Weibin Chen Lei Ding Xiuying Yang Hengfeng Yuan Qingmin Zeng |
| author_facet | Zengxin Jiang Zengxin Jiang Guobin Qi Wei Lu Hao Wang Defang Li Weibin Chen Lei Ding Xiuying Yang Hengfeng Yuan Qingmin Zeng |
| author_sort | Zengxin Jiang |
| collection | DOAJ |
| description | Osteoarthritis (OA) is a common degenerative joint disease. Effective drugs that can halt or decelerate osteoarthritis progression are still lacking. Omaveloxolone is a semisynthetic oleanane triterpenoid exerting antioxidative and anti-inflammatory effects. The present study aims to determine whether omaveloxolone has a therapeutic effect on OA. Chondrocytes were treated with interleukin (IL)-1β to establish an OA cell model in vitro. Indicators of cell viability, oxidative stress, inflammation, cell apoptosis and extracellular matrix (ECM) degradation were investigated. Proteins related to the Nuclear factor erythroid derived-2-related factor 2 (Nrf2)/antioxidant response element (ARE) and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signalling pathways were assessed using Western blotting. A destabilized medial meniscus surgery-induced OA rat model was used in vivo. Gait analysis, microcomputed tomography analysis, and histopathological and immunohistochemical analyses were performed to determine the therapeutic effect of omaveloxolone on attenuating osteoarthritis in vivo. The results showed that omaveloxolone exerts antioxidative, anti-inflammatory, antiapoptotic and anti-ECM degradation effects via activation of the Nrf2/ARE signalling pathway and inhibition of the NF-κB signalling pathway in chondrocytes in vitro and attenuates OA progression in vivo, suggesting that omaveloxolone may be a potential therapeutic agent for OA. |
| first_indexed | 2024-04-12T18:13:16Z |
| format | Article |
| id | doaj.art-abf4ec841a924c7da23083e4430ed899 |
| institution | Directory Open Access Journal |
| issn | 1663-9812 |
| language | English |
| last_indexed | 2024-04-12T18:13:16Z |
| publishDate | 2022-09-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pharmacology |
| spelling | doaj.art-abf4ec841a924c7da23083e4430ed8992022-12-22T03:21:45ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122022-09-011310.3389/fphar.2022.952950952950Omaveloxolone inhibits IL-1β-induced chondrocyte apoptosis through the Nrf2/ARE and NF-κB signalling pathways in vitro and attenuates osteoarthritis in vivoZengxin Jiang0Zengxin Jiang1Guobin Qi2Wei Lu3Hao Wang4Defang Li5Weibin Chen6Lei Ding7Xiuying Yang8Hengfeng Yuan9Qingmin Zeng10Department of Orthopaedics, Shanghai Jiaotong University Affiliated Sixth People’s Hospital, Shanghai, ChinaDepartment of Orthopedic Surgery, Fudan University Jinshan Hospital, Shanghai, ChinaDepartment of Orthopedic Surgery, Zhongshan Hospital, Fudan University, Shanghai, ChinaDepartment of Orthopedic Surgery, Shanghai TCM-Integrated Hospital Shanghai University of TCM, Shanghai, ChinaDepartment of Orthopedics, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, ChinaDepartment of Orthopedic Surgery, Fudan University Jinshan Hospital, Shanghai, ChinaDepartment of Orthopedic Surgery, Fudan University Jinshan Hospital, Shanghai, ChinaDepartment of Orthopedic Surgery, Fudan University Jinshan Hospital, Shanghai, ChinaDepartment of Radiology, Fudan University Jinshan Hospital, Shanghai, ChinaDepartment of Orthopaedics, Shanghai Jiaotong University Affiliated Sixth People’s Hospital, Shanghai, ChinaDepartment of Orthopedic Surgery, Fudan University Jinshan Hospital, Shanghai, ChinaOsteoarthritis (OA) is a common degenerative joint disease. Effective drugs that can halt or decelerate osteoarthritis progression are still lacking. Omaveloxolone is a semisynthetic oleanane triterpenoid exerting antioxidative and anti-inflammatory effects. The present study aims to determine whether omaveloxolone has a therapeutic effect on OA. Chondrocytes were treated with interleukin (IL)-1β to establish an OA cell model in vitro. Indicators of cell viability, oxidative stress, inflammation, cell apoptosis and extracellular matrix (ECM) degradation were investigated. Proteins related to the Nuclear factor erythroid derived-2-related factor 2 (Nrf2)/antioxidant response element (ARE) and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signalling pathways were assessed using Western blotting. A destabilized medial meniscus surgery-induced OA rat model was used in vivo. Gait analysis, microcomputed tomography analysis, and histopathological and immunohistochemical analyses were performed to determine the therapeutic effect of omaveloxolone on attenuating osteoarthritis in vivo. The results showed that omaveloxolone exerts antioxidative, anti-inflammatory, antiapoptotic and anti-ECM degradation effects via activation of the Nrf2/ARE signalling pathway and inhibition of the NF-κB signalling pathway in chondrocytes in vitro and attenuates OA progression in vivo, suggesting that omaveloxolone may be a potential therapeutic agent for OA.https://www.frontiersin.org/articles/10.3389/fphar.2022.952950/fullosteoarthritisomaveloxoloneNrf2NF-κBapoptosis |
| spellingShingle | Zengxin Jiang Zengxin Jiang Guobin Qi Wei Lu Hao Wang Defang Li Weibin Chen Lei Ding Xiuying Yang Hengfeng Yuan Qingmin Zeng Omaveloxolone inhibits IL-1β-induced chondrocyte apoptosis through the Nrf2/ARE and NF-κB signalling pathways in vitro and attenuates osteoarthritis in vivo Frontiers in Pharmacology osteoarthritis omaveloxolone Nrf2 NF-κB apoptosis |
| title | Omaveloxolone inhibits IL-1β-induced chondrocyte apoptosis through the Nrf2/ARE and NF-κB signalling pathways in vitro and attenuates osteoarthritis in vivo |
| title_full | Omaveloxolone inhibits IL-1β-induced chondrocyte apoptosis through the Nrf2/ARE and NF-κB signalling pathways in vitro and attenuates osteoarthritis in vivo |
| title_fullStr | Omaveloxolone inhibits IL-1β-induced chondrocyte apoptosis through the Nrf2/ARE and NF-κB signalling pathways in vitro and attenuates osteoarthritis in vivo |
| title_full_unstemmed | Omaveloxolone inhibits IL-1β-induced chondrocyte apoptosis through the Nrf2/ARE and NF-κB signalling pathways in vitro and attenuates osteoarthritis in vivo |
| title_short | Omaveloxolone inhibits IL-1β-induced chondrocyte apoptosis through the Nrf2/ARE and NF-κB signalling pathways in vitro and attenuates osteoarthritis in vivo |
| title_sort | omaveloxolone inhibits il 1β induced chondrocyte apoptosis through the nrf2 are and nf κb signalling pathways in vitro and attenuates osteoarthritis in vivo |
| topic | osteoarthritis omaveloxolone Nrf2 NF-κB apoptosis |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2022.952950/full |
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