Abstract
Bone mesenchymal stem cells (BMSCs) senescence contributes to age-related bone loss. The alveolar bone in jaws originates from neural crest cells and possesses significant site- and age-related properties. However, such intrinsic characteristics of BMSCs from alveolar bone (AB-BMSCs) and the underlying regulatory mechanisms still remain unknown. Here, we found that the expression of special AT-rich binding protein 2 (SATB2) in human AB-BMSCs significantly decreased with aging. SATB2 knockdown on AB-BMSCs from young donors displayed these aging-related phenotypes in vitro. Meanwhile, enforced SATB2 overexpression could rejuvenate AB-BMSCs from older donors. Importantly, satb2 gene- modified BMSCs therapy could prevent the alveolar bone loss during the aging of rats. Mechanistically, the stemness regulator Nanog was identified as the direct transcriptional target of SATB2 in BMSCs and functioned as a downstream mediator of SATB2. Collectively, our data reveal that SATB2 in AB-BMSCs associates with their age-related properties, and prevents AB-BMSCs senescence via maintaining Nanog expression. These findings highlight the translational potential of transcriptional factor-based cellular reprogramming for anti-aging therapy.
Highlights
The adult skeleton is a high-renewal organ undergoing continuous bone remodeling via bone formation by osteoblasts and bone resorption by osteoclasts
These results indicate that special AT‐rich binding protein 2 (SATB2) expression in AB-Bone mesenchymal stem cells (BMSCs) is decreased with aging, suggesting potential roles of SATB2 underlying aging-related properties of alveolar bone and BMSCs
Reduced SATB2 was critically involved in the age-related properties of BMSCs and Nanog was identified as a downstream effector of SATB2
Summary
The adult skeleton is a high-renewal organ undergoing continuous bone remodeling via bone formation by osteoblasts and bone resorption by osteoclasts. Accumulating evidence suggests that age-dependent decline in the quantity and functions of bone mesenchymal stem cells (BMSCs) are largely attributed to bone loss in the aged or postmenopausal skeleton [2]. The intrinsic properties of BMSCs such as senescence, osteogenic/adipogenic differentiation potential, and osteoclastogenesis activity were markedly changed during aging process and associated with skeletal aging and bone loss [4, 5]. These findings provide strong evidence that age-related changes of BMSCs compromise bone remodeling especially the bone regenerative potential, and contribute to bone loss
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