Low Expression of Selenoprotein S Promotes Osteogenic Differentiation in Bone Marrow Mesenchymal Stromal Cells

Selenium performs biological functions in the human body primarily through selenoproteins, which are known to play critical roles in bone metabolism. Normal osteogenic function is maintained by steady bone metabolism in the mandible. The role of selenoprotein S (SelS), one of the 25 identified selenoproteins, in osteogenic differentiation remains unclear. This study aimed to investigate whether SelS is involved in osteogenic differentiation and to analyze the effect of low expression of SelS on osteogenic differentiation. Osteogenic differentiation was induced in vitro, and the expression dynamics of SelS, Sp7 transcription factor (Sp7), and alkaline phosphatase (Alp) were analyzed using quantitative PCR (qPCR) and Western blotting. Lentivirus-mediated RNA interference (RNAi) was employed to achieve stable SelS knockdown. Alp activity was evaluated after osteogenic differentiation. Mandibular bone formation was evaluated by micro-CT scanning and histological staining (Masson's trichrome staining). Transcriptome sequencing and bioinformatics analysis were conducted to identify genes and pathways regulated by SelS low expression. During osteogenic differentiation, the expression of SelS protein decreased. After low expression of SelS, osteogenic differentiation was performed and the expression of Alp and Sp7 increased. Alp staining showed that the number of mineralized particles in the low expression SelS group increased, indicating that low expression of SelS enhanced the osteogenic differentiation ability of cells. Micro-CT and histological staining showed that the mandibular collagen synthesis and bone formation in the low expression SelS group were higher than those in the control group. Transcriptomic profiling identified 2268 differentially expressed genes (DEGs) under SelS low expression, suggesting that SelS may play a regulatory role by affecting the expression of these genes. Our data suggest that SelS expression is related to osteogenic differentiation. At low levels, SelS can promote osteogenic differentiation, collagen synthesis, and enhance bone formation.