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Ferulic acid promotes bone defect repair after radiation by maintaining the stemness of skeletal stem cells
- Source :
- Stem Cells Translational Medicine, Vol 10, Iss 8, Pp 1217-1231 (2021), Stem Cells Translational Medicine
- Publication Year :
- 2021
- Publisher :
- Wiley, 2021.
-
Abstract
- 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 SSCs by specific chemical inhibitors partially abolished the promotive effect of FA on SSC‐mediated bone regeneration. In summary, our findings reveal a novel function of FA in repairing irradiated bone defects by maintaining SSC stemness and suggest that the p38/MAPK and ERK/MAPK pathways contribute to SSC‐mediated tissue regeneration postradiation.<br />Irradiation caused significant impairment of skeletal stem cell (SSC) stemness via inactivation of MAPK pathways. Ferulic acid (FA) rescued the irradiated SSC partially via reactivated MAPK signaling.
- Subjects :
- 0301 basic medicine
MAPK/ERK pathway
endocrine system
Medicine (General)
Coumaric Acids
p38 mitogen-activated protein kinases
Cell
03 medical and health sciences
Mice
0302 clinical medicine
R5-920
Osteogenesis
Gene expression
medicine
Animals
tissue repair
Bone regeneration
bone defect
irradiation
QH573-671
Chemistry
Cell growth
Stem Cells
Cell Differentiation
Cell Biology
General Medicine
Cell biology
Blot
030104 developmental biology
medicine.anatomical_structure
Tissue‐specific Progenitor and Stem cells
skeletal stem cells
Stem cell
Cytology
030217 neurology & neurosurgery
Developmental Biology
ferulic acid
Subjects
Details
- Language :
- English
- ISSN :
- 21576564 and 21576580
- Volume :
- 10
- Issue :
- 8
- Database :
- OpenAIRE
- Journal :
- Stem Cells Translational Medicine
- Accession number :
- edsair.doi.dedup.....1bcf85a2e1343a436958ad68bf9627dc