강동현 (기초과학연구원, 서울대학교) | 한빛사논문 > 한빛사

한빛사논문

조회1,042

기초과학연구원, 서울대학교

CV File 175 kb

Nat. Commun., Published 09 February 2022; 13, 779 | https://doi.org/10.1038/s41467-022-28385-7 Selenophosphate synthetase 1 deficiency exacerbates osteoarthritis by dysregulating redox homeostasis

Donghyun Kang^1,2,9, Jeeyeon Lee ^1,2,9, Jisu Jung², Bradley A. Carlson³, Moon Jong Chang⁴, Chong Bum Chang⁵, Seung-Baik Kang⁴, Byung Cheon Lee ⁶, Vadim N. Gladyshev⁷, Dolph L. Hatfield³, Byeong Jae Lee^2,8,* & Jin-Hong Kim^1,2,8,*

¹Center for RNA Research, Institute for Basic Science, Seoul 08826, South Korea. ²Department of Biological Sciences, College of Natural Sciences, Seoul National University, Seoul 08826, South Korea. ³Mouse Cancer Genetics Program, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. ⁴Department of Orthopaedic Surgery, Seoul National University College of Medicine, Boramae Hospital, Seoul 07061, South Korea. ⁵Department of Orthopaedic Surgery, Seoul National University Bundang Hospital, Seongnam 13620, South Korea. ⁶Department of Biotechnology, College of Life Sciences and Biotechnology, Korea University, Seoul 02841, South Korea. ⁷Division of Genetics, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA 02115, USA. ⁸Interdisciplinary Program in Bioinformatics, Seoul National University, Seoul 08826, South Korea. ⁹These authors contributed equally: Donghyun Kang, Jeeyeon Lee.

^*Corresponding author.

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.

논문정보

형식Research article
게재일2022년 02월 (BRIC 등록일 2022-02-18)
연구진국내(교신)+국외 연구진
분야 생명과학 > 노화/암생물학

댓글 작성 로그인

CV 열람하기

연락처 보기