Ferulic Acid Promotes Bone Defect Repair After Radiation by Maintaining the Stemness of Skeletal Stem Cells

作者：Jia-Wu Liang, Peilin Li, Qian Wang, Song Liao, Wei Hu, Zhidong Zhao, Zhi‐Ling Li, Bo-Feng Yin, Ning Mao, Li Ding, Heng Zhu · 发表于：Stem Cells Translational Medicine · 年份：2021 · DOI：10.1002/sctm.20-0536 · 被引用次数：39 · 研究领域：Mesenchymal stem cell research、Management of metastatic bone disease、Cancer Cells and Metastasis

The reconstruction of irradiated bone defects after settlement of skeletal tumors remains a significant challenge in clinical applications. In this study, we explored radiation-induced skeletal stem cell (SSC) stemness impairments and rescuing effects of ferulic acid (FA) on SSCs in vitro and in vivo. The immunophenotype, cell renewal, cell proliferation, and differentiation of SSCs in vitro after irradiation were investigated. Mechanistically, the changes in tissue regeneration-associated gene expression and MAPK pathway activation in irradiated SSCs were evaluated. The regenerative capacity of SSCs in the presence of FA in an irradiated bone defect mouse model was also investigated. We found that irradiation reduced CD140a- and CD105-positive cells in skeletal tissues and mouse-derived SSCs. Additionally, irradiation suppressed cell proliferation, colony formation, and osteogenic differentiation of SSCs. The RNA-Seq results showed that tissue regeneration-associated gene expression decreased, and the Western blotting results demonstrated the suppression of phosphorylated p38/MAPK and ERK/MAPK in irradiated SSCs. Notably, FA significantly rescued the radiation-induced impairment of SSCs by activating the p38/MAPK and ERK/MAPK pathways. Moreover, the results of imaging and pathological analyses demonstrated that FA enhanced the bone repair effects of SSCs in an irradiated bone defect mouse model substantially. Importantly, inhibition of the p38/MAPK and ERK/MAPK pathways in S...