한빛사논문
- 조회701
Hyunsoo Kim1,2,12, Kyunghee Lee1,12, Jin Man Kim1, Mi Yeong Kim1, Jae-Ryong Kim3, Han-Woong Lee 4, Youn Wook Chung5, Hong-In Shin6, Taesoo Kim7, Eui-Soon Park8, Jaerang Rho8, Seoung Hoon Lee9, Nacksung Kim10, Soo Young Lee11, Yongwon Choi2 & Daewon Jeong1,*
1Department of Microbiology, Laboratory of Bone Metabolism and Control, Yeungnam University College of Medicine, Daegu, Korea. 2Departments of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA, USA. 3Department of Biochemistry and Molecular Biology, Smart-aging Convergence Research Center, Yeungnam University College of Medicine, Daegu, Korea. 4Department of Biochemistry, College of Life Science and Biotechnology, Yonsei University, Seoul, Korea. 5Severance Biomedical Science Institute, Yonsei University College of Medicine, Seoul, Korea. 6IHBR, Department of Oral Pathology, School of Dentistry, Kyungpook National University, Daegu, Korea. 7Herbal Medicine Research Division, Korea Institute of Oriental Medicine, Daejeon, Korea. 8Department of Microbiology and BK21 Bio Brain Center, Chungnam National University, Daejeon, Korea. 9Department of Oral Microbiology and Immunology, Wonkwang University School of Dentistry, Iksan, Korea. 10National Research Laboratory for Regulation of Bone Metabolism and Disease, Chonnam National University Medical School, Gwangju, Korea. 11Division of Life and Pharmaceutical Sciences, Department of Life Science, Center for Cell Signaling & Drug Discovery Research, College of Natural Sciences, Ewha Womans University, Seoul, Korea.
12These authors contributed equally: Hyunsoo Kim, Kyunghee Lee.
*Corresponding author
Abstract
Selenoproteins containing selenium in the form of selenocysteine are critical for bone remodeling. However, their underlying mechanism of action is not fully understood. Herein, we report the identification of selenoprotein W (SELENOW) through large-scale mRNA profiling of receptor activator of nuclear factor (NF)-κΒ ligand (RANKL)-induced osteoclast differentiation, as a protein that is downregulated via RANKL/RANK/tumour necrosis factor receptor-associated factor 6/p38 signaling. RNA-sequencing analysis revealed that SELENOW regulates osteoclastogenic genes. SELENOW overexpression enhances osteoclastogenesis in vitro via nuclear translocation of NF-κB and nuclear factor of activated T-cells cytoplasmic 1 mediated by 14-3-3γ, whereas its deficiency suppresses osteoclast formation. SELENOW-deficient and SELENOW-overexpressing mice exhibit high bone mass phenotype and osteoporosis, respectively. Ectopic SELENOW expression stimulates cell-cell fusion critical for osteoclast maturation as well as bone resorption. Thus, RANKL-dependent repression of SELENOW regulates osteoclast differentiation and blocks osteoporosis caused by overactive osteoclasts. These findings demonstrate a biological link between selenium and bone metabolism.
논문정보
- Research article
- 2021년 04월 (BRIC 등록일 2021-04-20)
- 국내(교신)+국외 연구진
- 의약학 > 분자세포의학
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