Selenoprotein W ensures physiological bone remodeling by preventing hyperactivity of osteoclasts

Hyunsoo Kim, Kyunghee Lee, Jin Man Kim, Mi Yeong Kim, Jae-Ryong Kim, Han-Woong Lee, Youn Wook Chung, Hong-In Shin, Taesoo Kim, Eui-Soon Park, Jaerang Rho, Seoung Hoon Lee, Nacksung Kim, Soo Young Lee, Yongwon Choi and Daewon Jeong ()
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Hyunsoo Kim: Yeungnam University College of Medicine
Kyunghee Lee: Yeungnam University College of Medicine
Jin Man Kim: Yeungnam University College of Medicine
Mi Yeong Kim: Yeungnam University College of Medicine
Jae-Ryong Kim: Yeungnam University College of Medicine
Han-Woong Lee: Yonsei University
Youn Wook Chung: Yonsei University College of Medicine
Hong-In Shin: Kyungpook National University
Taesoo Kim: Korea Institute of Oriental Medicine
Eui-Soon Park: Chungnam National University
Jaerang Rho: Chungnam National University
Seoung Hoon Lee: Wonkwang University School of Dentistry
Nacksung Kim: Chonnam National University Medical School
Soo Young Lee: Ewha Womans University
Yongwon Choi: University of Pennsylvania School of Medicine
Daewon Jeong: Yeungnam University College of Medicine

Nature Communications, 2021, vol. 12, issue 1, 1-13

Abstract: 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.

Date: 2021
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DOI: 10.1038/s41467-021-22565-7

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