Table_1_ASPH Regulates Osteogenic Differentiation and Cellular Senescence of BMSCs.XLSX

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 expressed ASPH gene in middle-aged and elderly aged groups which were obtained from GSE35955. Subsequent analysis in various databases, such as TCGA, GTEx, and CCLE, revealed that ASPH had positive correlations with several osteogenic markers. The depletion of mouse Asph suppressed the capacity of osteogenic differentiation in bone marrow mesenchymal stem cells (BMSCs). Notably, the expression of ASPH in vitro decreased during aging and senescence. The deficiency of Asph accelerated cellular senescence in BMSCs. Conversely, the overexpression of Asph enhanced the capacity of osteogenic differentiation and inhibited cellular senescence. Mechanistically, ASPH regulated Wnt signaling mediated by Gsk3β. Taken together, our data established that ASPH was 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.

骨髓间充质干细胞（BMSCs）的成骨分化与细胞衰老在年龄相关性骨丢失中发挥关键作用。然而，此类功能异常的具体诱因仍未明确。本研究从GSE35955数据集获取中老年人组样本，筛选得到差异表达的天冬氨酸β-羟化酶（ASPH）基因。后续通过TCGA、GTEx、CCLE等多个数据库开展分析，结果显示ASPH与多种成骨标志物呈正相关。敲低小鼠Asph基因可抑制骨髓间充质干细胞的成骨分化能力。值得注意的是，体外实验中ASPH的表达会随细胞衰老与机体衰老进程下调。Asph基因缺失会加速BMSCs的细胞衰老。反之，过表达Asph则可增强成骨分化能力并抑制细胞衰老。机制上，ASPH可调控由糖原合成激酶3β（Gsk3β）介导的Wnt信号通路。综上，本研究数据表明ASPH可能通过调控细胞衰老与成骨分化参与年龄相关性骨丢失的发病进程，为年龄相关性骨丢失的治疗提供了全新的研究视角。