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Selenophosphate synthetase 1 deficiency exacerbates osteoarthritis by dysregulating redox homeostasis

Author

Listed:
  • Donghyun Kang

    (Institute for Basic Science
    Seoul National University)

  • Jeeyeon Lee

    (Institute for Basic Science
    Seoul National University)

  • Jisu Jung

    (Seoul National University)

  • Bradley A. Carlson

    (National Institutes of Health)

  • Moon Jong Chang

    (Seoul National University College of Medicine, Boramae Hospital)

  • Chong Bum Chang

    (Seoul National University Bundang Hospital)

  • Seung-Baik Kang

    (Seoul National University College of Medicine, Boramae Hospital)

  • Byung Cheon Lee

    (Korea University)

  • Vadim N. Gladyshev

    (Brigham and Women’s Hospital and Harvard Medical School)

  • Dolph L. Hatfield

    (National Institutes of Health)

  • Byeong Jae Lee

    (Seoul National University
    Seoul National University)

  • Jin-Hong Kim

    (Institute for Basic Science
    Seoul National University
    Seoul National University)

Abstract

Aging and mechanical overload are prominent risk factors for osteoarthritis (OA), which lead to an imbalance in redox homeostasis. The resulting state of oxidative stress drives the pathological transition of chondrocytes during OA development. However, the specific molecular pathways involved in disrupting chondrocyte redox homeostasis remain unclear. Here, we show that selenophosphate synthetase 1 (SEPHS1) expression is downregulated in human and mouse OA cartilage. SEPHS1 downregulation impairs the cellular capacity to synthesize a class of selenoproteins with oxidoreductase functions in chondrocytes, thereby elevating the level of reactive oxygen species (ROS) and facilitating chondrocyte senescence. Cartilage-specific Sephs1 knockout in adult mice causes aging-associated OA, and augments post-traumatic OA, which is rescued by supplementation of N-acetylcysteine (NAC). Selenium-deficient feeding and Sephs1 knockout have synergistic effects in exacerbating OA pathogenesis in mice. Therefore, we propose that SEPHS1 is an essential regulator of selenium metabolism and redox homeostasis, and its dysregulation governs the progression of OA.

Suggested Citation

  • Donghyun Kang & Jeeyeon Lee & Jisu Jung & Bradley A. Carlson & Moon Jong Chang & Chong Bum Chang & Seung-Baik Kang & Byung Cheon Lee & Vadim N. Gladyshev & Dolph L. Hatfield & Byeong Jae Lee & Jin-Hon, 2022. "Selenophosphate synthetase 1 deficiency exacerbates osteoarthritis by dysregulating redox homeostasis," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-28385-7
    DOI: 10.1038/s41467-022-28385-7
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    References listed on IDEAS

    as
    1. Quanbo Ji & Xiaojie Xu & Lei Kang & Yameng Xu & Jingbo Xiao & Stuart B. Goodman & Xiang Zhu & Wenchao Li & Juan Liu & Xu Gao & Zhifeng Yan & Yuxuan Zheng & Zheng Wang & William J. Maloney & Qinong Ye , 2019. "Hematopoietic PBX-interacting protein mediates cartilage degeneration during the pathogenesis of osteoarthritis," Nature Communications, Nature, vol. 10(1), pages 1-15, December.
    2. Sukyeong Kim & Sangbin Han & Yeongjae Kim & Hyeon-Seop Kim & Young-Ran Gu & Donghyun Kang & Yongsik Cho & Hyeonkyeong Kim & Jeeyeon Lee & Yeyoung Seo & Moon Jong Chang & Chong Bum Chang & Seung-Baik K, 2019. "Tankyrase inhibition preserves osteoarthritic cartilage by coordinating cartilage matrix anabolism via effects on SOX9 PARylation," Nature Communications, Nature, vol. 10(1), pages 1-18, December.
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    Cited by:

    1. Nana Geng & Mengtian Fan & Biao Kuang & Fengmei Zhang & Menglin Xian & Lin Deng & Cheng Chen & Yiming Pan & Jianqiang Chen & Naibo Feng & Li Liang & Yuanlan Ye & Kaiwen Liu & Xiaoli Li & Yu Du & Fengj, 2024. "10-hydroxy-2-decenoic acid prevents osteoarthritis by targeting aspartyl β hydroxylase and inhibiting chondrocyte senescence in male mice preclinically," Nature Communications, Nature, vol. 15(1), pages 1-23, December.
    2. Ming-liang Ji & Hua Jiang & Zhuang Li & Rui Geng & Jun Zheng Hu & Yu Cheng Lin & Jun Lu, 2022. "Sirt6 attenuates chondrocyte senescence and osteoarthritis progression," Nature Communications, Nature, vol. 13(1), pages 1-18, December.

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