Gradual repression of selenoprotein W ensures physiological bone remodelling

Hyunsoo Kim, Kyunghee Lee, Jin Man Kim, Jae-Ryong Kim, Han-Woong Lee, Youn Wook Chung, Hong-In Shin, Eui-Soon Park, Jaerang Rho, Seoung Hoon Lee, Nacksung Kim, Soo Young Lee, Yongwon Choi & Daewon Jeong

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Received: 17th January 18

Selenoproteins containing selenium in the form of selenocysteine are critical for bone remodelling. However, their mechanism of action is not well understood. Here, 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 signalling. RNA sequencing analysis revealed that SELENOW regulates osteoclastogenic genes. SELENOW overexpression enhanced osteoclastogenesis in vitro via nuclear translocation of NF-kB and nuclear factor of activated T-cells cytoplasmic 1, whereas its loss suppressed osteoclast formation. SELENOW-deficient and SELENOW-overexpressing mice exhibited osteopetrosis and osteoporosis, respectively. Ectopic SELENOW expression stimulated cell-cell fusion critical for osteoclast maturation as well as bone resorption. Thus, RANKL-dependent repression of SELENOW maintains proper osteoclast differentiation and blocks osteoporosis caused by overactive osteoclasts. These findings demonstrate a biological link between selenium and bone metabolism.

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This is an abstract of a preprint hosted on an independent third party site. It has not been peer reviewed but is currently under consideration at Nature Communications.

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