Abstract
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.
Highlights
Osteoporosis is characterized by a reduction of bone mass and dysfunction of bone microarchitecture (Al Anouti et al, 2019; Yang et al, 2019)
Our study revealed Aspartate β-hydroxylase (ASPH) promoting the process of osteogenesis while inhibiting cellular senescence through regulating Gsk3β-mediated Wnt signaling, which potentially provided new insights for aged-related bone loss
Our data showed ASPH longest isoform promoting the osteogenesis while inhibiting cellular senescence, indicating it potentially results in an elevated capacity of bone formation
Summary
Osteoporosis is characterized by a reduction of bone mass and dysfunction of bone microarchitecture (Al Anouti et al, 2019; Yang et al, 2019). Individuals are susceptible to suffer from the age-related osteoporosis because of the loss of bone mass and strength caused by skeletal aging (Li et al, 2015, 2018; Yu et al, 2018; Xiao et al, 2020). Skeletal aging-associated bone loss can be traced back to bone marrow mesenchymal stem cells (BMSCs). BMSCs play a great role in bone formation because of their potential of selfrenewal and multi-lineage differentiation including osteogenic lineage (Li et al, 2018; Peng et al, 2019). BMSCs present with a reduced capacity of self-renewal and osteogenic lineage commitment, which thereby results in the aberrant age-dependent bone formation (Childs et al, 2015; Li H. et al, 2017)
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