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- Title
Selenoprotein W ensures physiological bone remodeling by preventing hyperactivity of osteoclasts.
- Authors
Kim, Hyunsoo; Lee, Kyunghee; Kim, Jin Man; Kim, Mi Yeong; Kim, Jae-Ryong; Lee, Han-Woong; Chung, Youn Wook; Shin, Hong-In; Kim, Taesoo; Park, Eui-Soon; Rho, Jaerang; Lee, Seoung Hoon; Kim, Nacksung; Lee, Soo Young; Choi, Yongwon; Jeong, Daewon
- 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. Selenoproteins containing selenium have a variety of physiological functions including redox homeostasis and thyroid hormone metabolism. Here, the authors show that RANKL-dependent repression of selenoprotein W regulates cell fusion during osteoclast differentiation and bone remodelling in mice.
- Subjects
BONE resorption; OSTEOCLASTS; OSTEOCLASTOGENESIS; BONE remodeling; NUCLEAR factor of activated T-cells; CELL fusion; BONE metabolism; SELENOPROTEINS
- Publication
Nature Communications, 2021, Vol 12, Issue 1, p1
- ISSN
2041-1723
- Publication type
Article
- DOI
10.1038/s41467-021-22565-7