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Hypoxia/reoxygenation activates the JNK pathway and accelerates synovial senescence

  • Authors:
    • Yubiao Zhang
    • Siqi Zhou
    • Weisong Cai
    • Guangtao Han
    • Jianping Li
    • Mao Chen
    • Haohuan Li
  • View Affiliations / Copyright

    Affiliations: Department of Orthopedics, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, P.R. China
    Copyright: © Zhang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 265-276
    |
    Published online on: April 30, 2020
       https://doi.org/10.3892/mmr.2020.11102
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Abstract

Hypoxia/reoxygenation (H/R) may play an important role via senescence in the mechanism of osteoarthritis (OA) development. The synovial membrane is highly sensitive to H/R due to its oxygen consumption feature. Excessive mechanical loads and oxidative stress caused by H/R induce a senescence‑associated secretory phenotype (SASP), which is related to the development of OA. The aim of the present study was to investigate the differences of SASP manifestation in synovial tissue masses between tissues from healthy controls and patients with OA. The present study used tumor necrosis factor‑α (TNF‑α) to pre‑treat synovial tissue and fibroblast‑like synoviocytes (FLS) to observe the effect of inflammatory cytokines on the synovial membrane before H/R. It was determined that H/R increased interleukin (IL)‑1β and IL‑6 expression levels in TNF‑α‑induced cell culture supernatants, increased the proportion of SA‑β‑gal staining, and increased the expression levels of high mobility group box 1, caspase‑8, p16, p21, matrix metalloproteinase (MMP)‑3 and MMP‑13 in the synovium. Furthermore, H/R opened the mitochondrial permeability transition pore, caused the loss of mitochondrial membrane potential (ΔΨm) and increased the release of reactive oxygen species (ROS). Moreover, H/R caused the expansion of the mitochondrial matrix and rupture of the mitochondrial extracorporeal membrane, with a decrease in the number of cristae. In addition, H/R induced activation of the JNK signaling pathway in FLS to induce cell senescence. Thus, the present results indicated that H/R may cause inflammation and escalate synovial inflammation induced by TNF‑α, which may lead to the pathogenesis of OA by increasing changes in synovial SASP and activating the JNK signaling pathway. Therefore, further studies expanding on the understanding of the pathogenesis of H/R etiology in OA are required.
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Spandidos Publications style
Zhang Y, Zhou S, Cai W, Han G, Li J, Chen M and Li H: Hypoxia/reoxygenation activates the JNK pathway and accelerates synovial senescence. Mol Med Rep 22: 265-276, 2020.
APA
Zhang, Y., Zhou, S., Cai, W., Han, G., Li, J., Chen, M., & Li, H. (2020). Hypoxia/reoxygenation activates the JNK pathway and accelerates synovial senescence. Molecular Medicine Reports, 22, 265-276. https://doi.org/10.3892/mmr.2020.11102
MLA
Zhang, Y., Zhou, S., Cai, W., Han, G., Li, J., Chen, M., Li, H."Hypoxia/reoxygenation activates the JNK pathway and accelerates synovial senescence". Molecular Medicine Reports 22.1 (2020): 265-276.
Chicago
Zhang, Y., Zhou, S., Cai, W., Han, G., Li, J., Chen, M., Li, H."Hypoxia/reoxygenation activates the JNK pathway and accelerates synovial senescence". Molecular Medicine Reports 22, no. 1 (2020): 265-276. https://doi.org/10.3892/mmr.2020.11102
Copy and paste a formatted citation
x
Spandidos Publications style
Zhang Y, Zhou S, Cai W, Han G, Li J, Chen M and Li H: Hypoxia/reoxygenation activates the JNK pathway and accelerates synovial senescence. Mol Med Rep 22: 265-276, 2020.
APA
Zhang, Y., Zhou, S., Cai, W., Han, G., Li, J., Chen, M., & Li, H. (2020). Hypoxia/reoxygenation activates the JNK pathway and accelerates synovial senescence. Molecular Medicine Reports, 22, 265-276. https://doi.org/10.3892/mmr.2020.11102
MLA
Zhang, Y., Zhou, S., Cai, W., Han, G., Li, J., Chen, M., Li, H."Hypoxia/reoxygenation activates the JNK pathway and accelerates synovial senescence". Molecular Medicine Reports 22.1 (2020): 265-276.
Chicago
Zhang, Y., Zhou, S., Cai, W., Han, G., Li, J., Chen, M., Li, H."Hypoxia/reoxygenation activates the JNK pathway and accelerates synovial senescence". Molecular Medicine Reports 22, no. 1 (2020): 265-276. https://doi.org/10.3892/mmr.2020.11102
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