| First Author | Kim H | Year | 2021 |
| Journal | Nat Commun | Volume | 12 |
| Issue | 1 | Pages | 2258 |
| PubMed ID | 33859201 | Mgi Jnum | J:317012 |
| Mgi Id | MGI:6713709 | Doi | 10.1038/s41467-021-22565-7 |
| Citation | Kim H, et al. (2021) Selenoprotein W ensures physiological bone remodeling by preventing hyperactivity of osteoclasts. Nat Commun 12(1):2258 |
| abstractText | 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)-kappaBeta 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-kappaB and nuclear factor of activated T-cells cytoplasmic 1 mediated by 14-3-3gamma, 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. |
