Rapamycin ameliorates senescence of periodontal ligament stem cells and promotes their osteogenesis via the PI3K/AKT pathway.
Abstract
Periodontal ligament stem cells (PDLSCs) have been regarded as ideal candidates for tissue regeneration due to their excellent self-renewal and multipotent differentiation ability. Rapamycin (RAPA) is reported to play an important role in the regulation of biological properties of stem cells and a variety of physiological processes. This study investigates whether RAPA could ameliorate the senescence and accelerate the osteogenic differentiation of PDLSCs, particularly the regenerative potential in a rat calvarial bone defect model, and the underlying mechanisms involved. β-galactosidase staining, quantitative real-time polymerase chain reaction, and western blot analysis were performed to assess the effects of RAPA on senescent PDLSCs. The osteogenic differentiation ability of PDLSCs was detected by alkaline phosphatase staining and activity, Alizarin Red S staining, and gene and protein levels of osteogenesis-related markers. The underlying signaling pathways were investigated via RNA transcriptome sequencing analysis and WB tests. Calvarial bone defects in rat were treated with PDLSCs pre-incubated with or without RAPA and/or H
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Research summary
Rapamycin improves the regenerative potential of periodontal ligament stem cells by reducing senescence and enhancing osteogenesis through the PI3K/AKT pathway. This study addresses the senescence of stem cells, which is a significant aspect of aging and longevity research, as it explores potential interventions to enhance tissue regeneration and combat age-related decline in stem cell function.
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