Selenophosphate synthetase 1 deficiency exacerbates osteoarthritis by dysregulating redox homeostasis

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 Hong Kim

Research output: Contribution to journalArticlepeer-review

35 Citations (Scopus)


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.

Original languageEnglish
Article number779
JournalNature communications
Issue number1
Publication statusPublished - 2022 Dec

Bibliographical note

Funding Information:
This work was supported by grants from the National Research Foundation of Korea (NRF-2015M3A9E6028674, NRF-2016R1A5A1010764, NRF-2017M3A9D8064193, NRF-2020R1A2C2012300, NRF-2021R1I1A1A01055626), the Institute for Basic Science from the Ministry of Science, ICT, and Future Planning of Korea (IBS-R008-D1), and Suh Kyungbae Foundation.

Publisher Copyright:
© 2022, The Author(s).

ASJC Scopus subject areas

  • General Chemistry
  • General Biochemistry,Genetics and Molecular Biology
  • General
  • General Physics and Astronomy


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