ASPHRegulates Osteogenic Differentiation and Cellular Senescence of BMSCs

Osteogenesis and senescence of BMSCs play great roles in age-related bone loss. However, the causes of these dysfunctions remain unclear. In this study, we identified a differentially expressedASPHgene in middle-aged and elderly aged groups which were obtained from GSE35955. Subsequent analysis in various databases, such as TCGA, GTEx, and CCLE, revealed thatASPHhad positive correlations with several osteogenic markers. The depletion of mouseAsphsuppressed the capacity of osteogenic differentiation in bone marrow mesenchymal stem cells (BMSCs). Notably, the expression ofASPH in vitrodecreased during aging and senescence. The deficiency ofAsphaccelerated cellular senescence in BMSCs. Conversely, the overexpression ofAsphenhanced the capacity of osteogenic differentiation and inhibited cellular senescence. Mechanistically,ASPHregulated Wnt signaling mediated by Gsk3 beta. Taken together, our data established thatASPHwas potentially involved in the pathogenesis of age-related bone loss through regulating cellular senescence and osteogenic differentiation, which provides some new insights to treat age-related bone loss.