Selenophosphate synthetase 1 deficiency exacerbates osteoarthritis by dysregulating redox homeostasis.

Autor: Kang D; Center for RNA Research, Institute for Basic Science, Seoul, 08826, South Korea.; Department of Biological Sciences, College of Natural Sciences, Seoul National University, Seoul, 08826, South Korea., Lee J; Center for RNA Research, Institute for Basic Science, Seoul, 08826, South Korea.; Department of Biological Sciences, College of Natural Sciences, Seoul National University, Seoul, 08826, South Korea., Jung J; Department of Biological Sciences, College of Natural Sciences, Seoul National University, Seoul, 08826, South Korea., Carlson BA; Mouse Cancer Genetics Program, National Cancer Institute, National Institutes of Health, Bethesda, MD, 20892, USA., Chang MJ; Department of Orthopaedic Surgery, Seoul National University College of Medicine, Boramae Hospital, Seoul, 07061, South Korea., Chang CB; Department of Orthopaedic Surgery, Seoul National University Bundang Hospital, Seongnam, 13620, South Korea., Kang SB; Department of Orthopaedic Surgery, Seoul National University College of Medicine, Boramae Hospital, Seoul, 07061, South Korea., Lee BC; Department of Biotechnology, College of Life Sciences and Biotechnology, Korea University, Seoul, 02841, South Korea., Gladyshev VN; Division of Genetics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, 02115, USA., Hatfield DL; Mouse Cancer Genetics Program, National Cancer Institute, National Institutes of Health, Bethesda, MD, 20892, USA., Lee BJ; Department of Biological Sciences, College of Natural Sciences, Seoul National University, Seoul, 08826, South Korea. imbglmg@snu.ac.kr.; Interdisciplinary Program in Bioinformatics, Seoul National University, Seoul, 08826, South Korea. imbglmg@snu.ac.kr., Kim JH; Center for RNA Research, Institute for Basic Science, Seoul, 08826, South Korea. jinhkim@snu.ac.kr.; Department of Biological Sciences, College of Natural Sciences, Seoul National University, Seoul, 08826, South Korea. jinhkim@snu.ac.kr.; Interdisciplinary Program in Bioinformatics, Seoul National University, Seoul, 08826, South Korea. jinhkim@snu.ac.kr.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2022 Feb 09; Vol. 13 (1), pp. 779. Date of Electronic Publication: 2022 Feb 09.
DOI: 10.1038/s41467-022-28385-7
Abstrakt: 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.
(© 2022. The Author(s).)
Databáze: MEDLINE
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