Abstract
ABSTRACTObjective: Resveratrol has been confirmed to improve bone quality and delay osteoporosis, but the mechanisms have not been thoroughly elucidated. In this report, we investigated the osteogenic differentiation effect of resveratrol on senescent bone mesenchymal stem cells (BMSCs) and the involvement of AMP-activated protein kinase (AMPK)/ reactive oxygen species (ROS) signaling pathway.Methods: Cell senescence, viability, and osteogenic differentiation of BMSCs influenced by resveratrol were investigated and ROS production and AMPK expression were detected.Results: Cell senescence, characterized by senescence β-galactosidase staining and senescence-related genes (p16, p21, and p53) expression, was attenuated by resveratrol. Cell viability, extracellular matrix calcification, and osteogenic-related genes expression were significantly enhanced after resveratrol treatment. ROS production in BMSCs was inhibited while AMPK expression was up-regulated by resveratrol. Inhibition of AMPK expression by compound C reduced resveratrol-prompted osteogenesis and ROS production down-regulation.Conclusion: These results provide a potential mechanism involving AMPK activation/ROS inhibition signaling pathway in osteogenic differentiation of BMSCs enhanced by resveratrol. It suggests that development of therapy towards ROS is an effective way for osteoporosis treatment.
Highlights
Osteoporosis, an age-related degenerative disease characterized by the loss of bone mass and the structural deterioration of bone tissue, has become a social problem along with the exacerbation of global population aging [1]
The lowest senescent cell ratio was observed at 25 μg/mL resveratrol, showing a 96% decrease compared to negative control (NC) group
The results showed that the endogenous reactive oxygen species (ROS) in senescent Bone mesenchymal stem cells (BMSCs) significantly decreased while calcified extracellular matrix increased at 25 μg/mL resveratrol compared to NC group
Summary
Osteoporosis, an age-related degenerative disease characterized by the loss of bone mass and the structural deterioration of bone tissue, has become a social problem along with the exacerbation of global population aging [1]. The imbalance between the bone formation activity of osteoblasts and the bone resorption activity of osteoclasts is considered as an important reason for bone loss [2]. Bone mesenchymal stem cells (BMSCs) are considered the progenitors for osteoblasts, but, BMSCs will undergo a replicative senescence ‘Hayflick limit’ with generations of cell division [3]. The biological functions of residual MSCs progressively decline and become susceptible to the accumulation of cellular damage and senescence. The senescent BMSCs exhibit lower osteogenic differentiation and higher adipogenic differentiation [4,5].
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