Hydrogen (H2) Alleviates Osteoarthritis by Inhibiting Apoptosis and Inflammation via the JNK Signaling Pathway
Hongwei Lu,1– 3,* Wei Wang,1– 3,* Xiaodiao Kang,1– 3,* Zeng Lin,1– 3 Jun Pan,1– 3 Shaowen Cheng,4 Jingdong Zhang1– 3 1Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical Uni...
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| Format: | Article |
| Language: | English |
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Dove Medical Press
2021-04-01
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| Series: | Journal of Inflammation Research |
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| Online Access: | https://www.dovepress.com/hydrogen-h2-alleviates-osteoarthritis-by-inhibiting-apoptosis-and-infl-peer-reviewed-article-JIR |
| _version_ | 1818431981904461824 |
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| author | Lu H Wang W Kang X Lin Z Pan J Cheng S Zhang J |
| author_facet | Lu H Wang W Kang X Lin Z Pan J Cheng S Zhang J |
| author_sort | Lu H |
| collection | DOAJ |
| description | Hongwei Lu,1– 3,* Wei Wang,1– 3,* Xiaodiao Kang,1– 3,* Zeng Lin,1– 3 Jun Pan,1– 3 Shaowen Cheng,4 Jingdong Zhang1– 3 1Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325000, People’s Republic of China; 2The Second School of Medicine, Wenzhou Medical University, Wenzhou, People’s Republic of China; 3Bone Research Institute, The Key Orthopaedic Laboratory of Zhejiang Province, Wenzhou, People’s Republic of China; 4Trauma Center, First Affiliated Hospital of Hainan Medical University, Haikou, People’s Republic of China*These authors contributed equally to this workCorrespondence: Shaowen ChengTrauma Center, First Affiliated Hospital of Hainan Medical University, 31 Long Hua Road, Haikou, 571100, People’s Republic of ChinaEmail chengshaowwn1@126.comJingdong ZhangDepartment of Orthopaedics, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, 109 Xue Yuan Xi Road, Wenzhou, Zhejiang, 325000, People’s Republic of ChinaTel +86-13587694869Email zjd4869@163.comBackground: Osteoarthritis (OA) is a very common condition and leads to joint pain, disability, and price tag all over the world. Pathogenesis of OA is closely related to numerous inflammatory and apoptosis cytokines. Hydrogen (H2) reportedly exhibits a diversity of effects such as anti-apoptotic, anti-inflammatory, and anti-oxidative properties via the JNK pathway. However, it is unknown whether H2 has a protective effect against OA via the JNK signaling pathway. Therefore, the aim of this study was to figure out whether hydrogen has protective effect on chondrocyte and further explore the possible underlying mechanism.Methods: The chondrocytes were obtained from the human cartilage tissues. Cells were stimulated by TBHP and treated with hydrogen. In vitro treatment effects were evaluated by Western blot assay, real-time PCR, immunofluorescence and TUNEL method. We conducted mice model of destabilization of the medial meniscus (DMM) and treated with hydrogen. In vivo treatment effects were evaluated by X-ray imaging assay, safranin O (SO) staining, TUNEL staining and immunohistochemical assay.Results: Our results showed that hydrogen can inhibit inflammatory factors (ADAMTS5 and MMP13) and apoptosis factors (cleaved caspase-3, cytochrome c, and Bax) in TBHP-induced chondrocytes. Furthermore, hydrogen can suppress the activation of JNK signaling pathway, whereas the effect of hydrogen can be abolished by anisomycin (a JNK activator). In vivo results showed that hydrogen can down-regulate the expression of p-JNK and cleaved caspase-3 expression.Conclusion: We uncovered that hydrogen (H2) could alleviate apoptosis response and ECM degradation in human chondrocytes via inhibiting the activation of the JNK signaling pathway. Meanwhile, in the surgically-induced DMM mice model, treatment with hydrogen (H2) performed a significant role in OA progression.Keywords: hydrogen, osteoarthritis, apoptosis, inflammation, JNK pathway |
| first_indexed | 2024-12-14T15:57:57Z |
| format | Article |
| id | doaj.art-e32d1120976f4127bf7ad119924f33ae |
| institution | Directory Open Access Journal |
| issn | 1178-7031 |
| language | English |
| last_indexed | 2024-12-14T15:57:57Z |
| publishDate | 2021-04-01 |
| publisher | Dove Medical Press |
| record_format | Article |
| series | Journal of Inflammation Research |
| spelling | doaj.art-e32d1120976f4127bf7ad119924f33ae2022-12-21T22:55:14ZengDove Medical PressJournal of Inflammation Research1178-70312021-04-01Volume 141387140263865Hydrogen (H2) Alleviates Osteoarthritis by Inhibiting Apoptosis and Inflammation via the JNK Signaling PathwayLu HWang WKang XLin ZPan JCheng SZhang JHongwei Lu,1– 3,* Wei Wang,1– 3,* Xiaodiao Kang,1– 3,* Zeng Lin,1– 3 Jun Pan,1– 3 Shaowen Cheng,4 Jingdong Zhang1– 3 1Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325000, People’s Republic of China; 2The Second School of Medicine, Wenzhou Medical University, Wenzhou, People’s Republic of China; 3Bone Research Institute, The Key Orthopaedic Laboratory of Zhejiang Province, Wenzhou, People’s Republic of China; 4Trauma Center, First Affiliated Hospital of Hainan Medical University, Haikou, People’s Republic of China*These authors contributed equally to this workCorrespondence: Shaowen ChengTrauma Center, First Affiliated Hospital of Hainan Medical University, 31 Long Hua Road, Haikou, 571100, People’s Republic of ChinaEmail chengshaowwn1@126.comJingdong ZhangDepartment of Orthopaedics, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, 109 Xue Yuan Xi Road, Wenzhou, Zhejiang, 325000, People’s Republic of ChinaTel +86-13587694869Email zjd4869@163.comBackground: Osteoarthritis (OA) is a very common condition and leads to joint pain, disability, and price tag all over the world. Pathogenesis of OA is closely related to numerous inflammatory and apoptosis cytokines. Hydrogen (H2) reportedly exhibits a diversity of effects such as anti-apoptotic, anti-inflammatory, and anti-oxidative properties via the JNK pathway. However, it is unknown whether H2 has a protective effect against OA via the JNK signaling pathway. Therefore, the aim of this study was to figure out whether hydrogen has protective effect on chondrocyte and further explore the possible underlying mechanism.Methods: The chondrocytes were obtained from the human cartilage tissues. Cells were stimulated by TBHP and treated with hydrogen. In vitro treatment effects were evaluated by Western blot assay, real-time PCR, immunofluorescence and TUNEL method. We conducted mice model of destabilization of the medial meniscus (DMM) and treated with hydrogen. In vivo treatment effects were evaluated by X-ray imaging assay, safranin O (SO) staining, TUNEL staining and immunohistochemical assay.Results: Our results showed that hydrogen can inhibit inflammatory factors (ADAMTS5 and MMP13) and apoptosis factors (cleaved caspase-3, cytochrome c, and Bax) in TBHP-induced chondrocytes. Furthermore, hydrogen can suppress the activation of JNK signaling pathway, whereas the effect of hydrogen can be abolished by anisomycin (a JNK activator). In vivo results showed that hydrogen can down-regulate the expression of p-JNK and cleaved caspase-3 expression.Conclusion: We uncovered that hydrogen (H2) could alleviate apoptosis response and ECM degradation in human chondrocytes via inhibiting the activation of the JNK signaling pathway. Meanwhile, in the surgically-induced DMM mice model, treatment with hydrogen (H2) performed a significant role in OA progression.Keywords: hydrogen, osteoarthritis, apoptosis, inflammation, JNK pathwayhttps://www.dovepress.com/hydrogen-h2-alleviates-osteoarthritis-by-inhibiting-apoptosis-and-infl-peer-reviewed-article-JIRhydrogenosteoarthritisapoptosisinflammationjnk pathway |
| spellingShingle | Lu H Wang W Kang X Lin Z Pan J Cheng S Zhang J Hydrogen (H2) Alleviates Osteoarthritis by Inhibiting Apoptosis and Inflammation via the JNK Signaling Pathway Journal of Inflammation Research hydrogen osteoarthritis apoptosis inflammation jnk pathway |
| title | Hydrogen (H2) Alleviates Osteoarthritis by Inhibiting Apoptosis and Inflammation via the JNK Signaling Pathway |
| title_full | Hydrogen (H2) Alleviates Osteoarthritis by Inhibiting Apoptosis and Inflammation via the JNK Signaling Pathway |
| title_fullStr | Hydrogen (H2) Alleviates Osteoarthritis by Inhibiting Apoptosis and Inflammation via the JNK Signaling Pathway |
| title_full_unstemmed | Hydrogen (H2) Alleviates Osteoarthritis by Inhibiting Apoptosis and Inflammation via the JNK Signaling Pathway |
| title_short | Hydrogen (H2) Alleviates Osteoarthritis by Inhibiting Apoptosis and Inflammation via the JNK Signaling Pathway |
| title_sort | hydrogen h2 alleviates osteoarthritis by inhibiting apoptosis and inflammation via the jnk signaling pathway |
| topic | hydrogen osteoarthritis apoptosis inflammation jnk pathway |
| url | https://www.dovepress.com/hydrogen-h2-alleviates-osteoarthritis-by-inhibiting-apoptosis-and-infl-peer-reviewed-article-JIR |
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